Chapter
29
Anatomy of the Tongue and Taste Buds Martin Witt and Klaus Reutter
29.1
INTRODUCTION
“ … Many papillae are evident, I might say, innumerable, and the appearance is so elegant that they catch the view and thoughts of the observer, and control him for a long time and not without enjoyment … All this delights the curious mind, when observing with an engyscope; and if anyone asks to what they are similar, I am unsure whether I should compare this huge number of papillae first with grapes or fruits of the bay, or innumerable mushrooms emerging between fine, densely standing blades of grass …” These are the first detailed and enthusiastic words on papillae and their “membranes” in human tongues by Lorenzo Bellini (1665) (Figure 29.1), who knew that Marcello Malpighi (1628–94) had reported on lingual papillae the year before. Malpighi discovered mucosal elevations associated with nerve fibers, naming these elevations “papillae,” as the morphological substrates for gustatory sensation (Figure 29.2). The peripheral taste apparatus includes the gustatory sensory organs or taste buds and their innervation, and the specific papillae within which taste buds are assembled. What one needs to know about taste buds in relation to how one perceives tastants depends on the approach to taste perception. One aim of this chapter is to provide a sufficient knowledge on peripheral gustatory anatomy as a basis for understanding other chapters of this book. Some structural details about the human peripheral taste system are well known, but it is also worthwhile to provide comparative anatomical information to fill in the gaps or understand and establish basic principles. The fundamental question of how tastants are perceived has been addressed for more than two millenia, and the majority of concepts, theories, and experimental “proofs” that have been proposed have since given
way to present-day concepts. This chapter incorporates this rich history which sculpted our contemporary views of gustatory anatomy and physiology. Aristotle (384–322 BC), applying Platonic concepts, argued that taste sensation was carried from the tongue via the blood, to the liver or heart, which was the common seat of the soul and all sense perception [De sensu 438b 26; On youth and old age, 469a 5–13; cited after Siegel (1970)]. Galen’s (Claudius Galenus, 129–201 AD) anatomical analyses challenged this notion: his detailed studies on the innervation of the tongue describe correctly the different functions of the three principal nerves supplying the tongue (lingual, glossopharyngeal, and hypoglossal nerves), and demonstrate their origin at the base of the brain. Galen posited that the lingual nerve communicated gustatory sensations, a concept yet resonant in contemporary neurobiology. One strand of nerve fibers corresponding to cranial nerve IX (CN IX or glossopharyngeal nerve) of present terminology (rediscovered in humans by Panizza, 1834 was already known to Galen as the principal gustatory nerve of the tongue. CN IX also carries some motor fibers to the pharynx. Galen also noted excretory ducts of the lingual and sub-mandibular glands (in ox). The particular structure of the tongue surface was initially described by Casserius (1609) and, later by Malpighi (1686) and Bellini (1665) (reviewed by Jurisch, 1922. Further evidence for the significance of the papillary epithelium and its cells came from observations in taste organs of the frog (Fixsen, 1857, Waller, 1847, 1849). Taste buds were identified initially on the barbels and skin of fishes by Leydig (1851) and described as “becherförmige Organe” (goblet-shaped organs), whose function he associated with tactile sensitivity. Schulze (1863) subsequently suggested they were chemosensory structures. Similar organs in mammals were described as Schmeckbecher (taste goblets)
Handbook of Olfaction and Gustation, Third Edition. Edited by Richard L. Doty. © 2015 Richard L. Doty. Published 2015 by John Wiley & Sons, Inc.
637
638
Chapter 29
Anatomy of the Tongue and Taste Buds
Figure 29.1 The cover sheet of Lorenzo Bellini’s book that summarizes examinations on the anatomy of the kidney and the taste organ. (Langerack, Leiden, 1711).
Figure 29.2 Depiction of a bovine tongue by Marcello Malpighi (1686) showing “patches” where papillae were observed. Note the concentration of fungiform papillae (dots) on the tip of the tongue. The drawing of vallate and foliate papillae is still rather vague.
(Lovén, 1868) and Geschmacksknospen (taste buds) or Geschmackszwiebeln (“taste onions”) (Schwalbe, 1868). Herrick (1904) translated “Geschmackskospen” as “taste buds.” Their location within lingual papillae, the latter already associated with the loci of taste perception, lent credence to their identity as taste sensor organs.
Nineteenth-century studies focused on cytological features, nerve supply (Figures 29.3 and 29.5), and the development of taste buds. While the nerve-dependent nature of taste sensation was known since Galen’s time, its significance for sensory organ physiology blossomed in the mid-1800s. With development of the neuron doctrine (see Koelliker, 1844), previously described “ganglion globules” (Ganglienkugeln: Ehrenberg, 1833) could now be acknowledged as part of a specialized cellular system (cell theory of Schleiden and Schwann) (Schwann, 1839). Two major prerequisites favored the expansion of scientific knowledge in the nineteenth century: (1) replacement of the often speculative natural philosophy by the experimentally based natural sciences, mainly represented by Francois Magendie (1783–1855) in France and Johannes Müller (1801–58) in Germany, and (2) technical advances which included improved microscopes (K. Zeiss, 1816–88, together with Ernst Abbé, 1840–1905, and E. Leitz, 1843–1920) as well as use of histological techniques, for example, introduction of chromic acid for histological examination of neural tissue (Hannover, 1840), allowing for the distinction between cells and fibers. Further, gold chloride staining facilitated discriminating finely ramifying nerve fibers (Gerlach, 1858). Helmholtz (1842) observed a direct continuity between nerve cells (globuli gangliosi) and their fibers in evertebrates. The demand for the neuron doctrine in vertebrates was established by Koelliker (1844). Introduction of the methylene blue staining method facilitated observations that fine nerve fibers in the frog taste disc widened with varicosities, penetrated the gustatory epithelium and approached the sensory cells “with extremely sharp small knobs, [which] … connect taste cells not continuously, but per contiguitatem” (Ehrlich, 1886). This pioneering observation of secondary sensory cells in a taste organ that was clearly different from primary sensory cells, as had already been described in the olfactory epithelium, albeit without the understanding of the “contact” nature of taste bud cells and their innervating afferents, as later described ultrastructurally, was opposed by Retzius (1892). Using the Golgi silver impregnation method (Golgi, 1873), Retzius attributed a sensory function only to free nerve endings (Figure 29.5b). Later, Krause (1911) clearly demonstrated that the finest nerve fibers enter the taste bud and ascend to the taste pore, but do not merge with taste bud cells whose basal processes end near the basal cells.
29.2 LINGUAL PAPILLAE AND TASTE BUD DISTRIBUTION 29.2.1
Nongustatory Papillae
Approximately 60 years before taste buds were identified as gustatory organs, an illustration of the human tongue
29.2 Lingual Papillae and Taste BUD Distribution
(a)
639 (b)
Figure 29.3 These illustrations of Bourgery and Jacob (1839) show the human tongue including nerve and blood supply, as well as the lingual muscle system. In spite of precise macroscopical observations on the innervation of glands and muscles, it still represents indirectly the (nowadays revised) morphological concept of gustation in the early nineteenth century, according to which the principal taste nerves are the lingual (p in (a) and (b); CN V3 ) and glossopharyngeal (t in (b); CN IX) nerves. The chorda tympani, although depicted near the submandibular ganglion (q in (a) and (b); CT), does not reach the lingual dorsum. Ebner’s glands are not known to the authors. (a): D, submandibular gland with q, chorda tympani and submandibular ganglion and p, lingual nerve; s, hypoglossal nerve (CN XII); E, sublingual gland; F, Nuhn’s gland. (b): C styloid process; b, stylopharyngeus muscle, the leading muscle for t, glossopharyngeal nerve (CN IX), which overlaps partly with the innervation area of the lingual nerve; k, lingual artery; p, lingual nerve, interrupted to show the glossopharyngeal nerve; q, part of the chorda tympani nerve; s, hypoglossal nerve (CN XII); X, trunk of the facial nerve. (See plate section for color version.)
by Sömmering (1806) (Figure 29.4) accurately showed the regional distribution of lingual papillae. A line called the sulcus terminalis (an ontogenetic remnant, see below), which is located posterior to the vallate papillae, separates the body of the tongue from the lingual root. It may be seen that the sulcus terminalis extends laterally to the pharyngeal wall from the foramen caecum (also an ontogenetic remnant) near the midline (see Figures 29.4 and 29.11). The root of the tongue is covered by a papilla- free smooth epithelium, and beneath this epithelium lie mucous glands and a reticular connective tissue filled with lymphatic follicles which lead to the designation of “lingual tonsil.” Ducts of intralingual salivary glands (Ebner, 1873) empty into the troughs of vallate and foliate papillae (see below). The dorsal surface of the tongue is covered with filiform and conical papillae from the sulcus terminalis to the tongue tip. Filiform papillae are the most prevalent type, while the number of conical papillae may vary. Both types of papillae are sparse along the lingual margin and abundant in the middle regions. Conical papillae have a cylindrical base, and taper to a sharp point at their apex. Filiform papillae (L. filum = thread) have a pyramidal shape, and a narrow tail of cornified cells extending from their apical
tips as a pennant. The fila are part of the fibrous mat on the tongue’s surface in the hypertrophic condition called “hairy tongue.”
29.2.2
Gustatory Papillae
Taste buds occur in distinct papillae of the tongue, the epithelium of the palate, oropharynx, larynx (epiglottis), and the upper esophagus. Taste buds of most vertebrates are bulb-shaped structures which are composed of about 50–120 bipolar cells (see Figures 29.9 and 29.10). With the exception of basal cells, the slender taste bud cells arise from an interrupted basal membrane and converge with their apical protrusions, the microvilli, into the mucus-filled taste pit. Together, these cells form the organ’s sensory epithelium. The nuclei of the cells are located in the lower third of the taste bud, which is approximately the region where most afferent nerve fiber terminals are distributed. Sensory cells possess transmembrane receptors and/or ion channels for specific taste stimuli at apical and lateral portions of the cell membrane. Taste buds are demarcated from
640
Chapter 29
Anatomy of the Tongue and Taste Buds
surrounding nongustatory epithelial cells by specialized epithelial cells (marginal cells).
29.2.2.1 Distribution of Lingual Taste Buds.
The pattern of taste bud distribution over the tongue surface is similar among humans and other mammals. Lingual taste buds are found exclusively within gustatory papillae, that is, those bearing taste buds. Similar types of gustatory papillae are located on homologous regions of adult mammalian tongues. The gustatory papillae include the vallate, foliate, and fungiform papillae. As the term suggests, typical fungiform papillae are mushroom-shaped, with a slender neck and an enlarged head (Figures 29.6–29.8). But the majority of fungiform papillae vary in form and the filiform papillae are intermingled among them. Shortly after the published discovery of taste buds in humans (Lovén, 1868; Schwalbe, 1868), the first systematic investigations on the distribution of human taste buds within the oral cavity were carried out by the medical student Hoffmann (1875). He emphasized that taste buds are more sparse within foliate papillae and the soft palate including the uvula. Hoffmann concluded that the development of taste perception is dependent on the number of taste buds on a particular location. Of the approximately 4,600 total taste buds in all three lingual fields in humans, vallate buds comprise about 48% (2200), foliates about 28% (1280) and fungiforms 24% (1120). However, taste bud numbers vary greatly among individuals (Miller and Reedy, 1990a), with some adults possessing a total of only 500 taste buds
Figure 29.4 The first precise depiction of a human tongue by Samuel Sömmering (1806). (Above) The anterior part (left side) of the tongue shows numerous fungiform papillae. Behind the V-like arrangement of vallate papillae (right side), the lingual tonsils and the intrance to larynx with the epiglottis are visible. (Below) Lateral view of the tongue shows the left lingual artery and its ramifications into gustatory papillae, which appear as red dots after injection of the artery with a red dye (observation of Sömmering).
d
c
b
e
sp
sp
g
a
f bz
(a)
(b)
Figure 29.5 (a) First description of a mammalian taste bud (vallate papilla of the swine) by Schwalbe (1868). Minor bundles and fibrils of nerves are lost in the “interior of taste goblets”. Note the incorrect arrangement of basal cells. According to Schwalbe, two cell types, pin cells (Stiftchenzellen), and rod cells (Stabzellen), might mediate different taste sensations. (b) Distinguished observation of intra- and intergemmal nerve terminals in the rabbit foliate papillae by Retzius (1892) using the Golgi silver impregnation method. Taste buds are directed to the trench of the papilla. Retzius also depicts a slender bipolar “sensory” intragemmal cell and a multipolar cell (bz) (right side). Direct contacts between nerve fibers and taste cells were not noticed. Retzius believed that exclusively nerve fibers rather than taste cells were responsible for gustatory sensations.
641
29.2 Lingual Papillae and Taste BUD Distribution
(a)
(b)
(c)
Figure 29.6 (a)–(c). Schematic drawings of taste bud-bearing, mammalian lingual papillae (longitudinal sections). (a) Fungiform papilla (papilla fungiformis) with two apically situated taste buds and their innervation. On the right side, a (taste bud- free) filiform papilla. (b) Foliate papillae (pp. foliatae). (c) Vallate papilla (p. vallata). In B and C, the taste buds are directed to the lateral trenches of the papillae. Serous Ebner glands drain to the trenches. Dermal connective tissue is rich in nerve fibers; below the taste buds they form subgemmal plexus.
(a)
Figure 29.7 Human fungiform papilla during development, week 15. Only one taste pore is visible (arrow). Scale bar = 50 μm. (b)
Figure 29.8 In vivo confocal laser scanning microscopy of a human fungiform taste bud. (a) 3D-reconstruction of a single taste bud. (b) The taste bud contours were delineated that allows the calculation of the taste bud volume. From Srur et al. (2010). (See plate section for color version.)
642
Chapter 29
Anatomy of the Tongue and Taste Buds
(Linden, 1993). The taste bud density of foliate papillae seems to be constant in life (Hou-Jensen, 1933), but age-related differences have been reported for vallate papillae, which are more numerous and containing more taste buds in younger individuals (Jurisch, 1922). There are also more marginal fungiform papillae during the late fetal and newborn period, but they usually lack taste buds and are referred to as “sucking papillae” (Habermehl, 1952; Yamasaki and Takahashi, 1982).
29.2.2.2 Vallate Papillae. Vallate papillae, first
comprehensively described by Haller (1766) and Sömmering (1806), lie directly anterior to the sulcus terminalis and extend in a V-shaped line across the root of the tongue (Figures 29.4 and 29.12). They are round and measure between 2 and 8 mm in diameter. The pores of taste buds open into the trenches around the bases of each vallate papilla (Figure 29.6). The papillae are innervated by an enormously large nerve fiber plexus originating from CN IX (see below) compared to foliate or fungiform papillae. The number of vallate papillae per human tongue varies between 4 and 18 (n = 2,264 tongues), with an average of 9.2 ±1.8 papillae (Münch, 1896). Ninety-eight percent of all tongues have a central median papilla (Figure 29.4). The presence of three or four lateral papillae on each tongue half was observed most often (20%). Atrophic changes were observed in papillae of some men > 40 years old and some women > 55–60 years old, though Jurisch (1922) reported that the number of vallate papillae did not appear to change systematically as a function of age. The average numbers of taste buds per papilla are summarized in Table 29.1.
29.2.2.3 Foliate
Papillae. Foliate papillae in
humans were first reported by Albinus (1754) and histologically described by Hönigschmied (1873), but did not become the focus of scientific attention in humans until the
twentieth century. These papillae, located bilaterally along the posterolateral margins of the tongue surface, consist of parallel rows of ridges (folia) and valleys which lie adjacent to the lower molar teeth. Ducts located between the folia transmit secretions from mostly serous lingual glands within the root of the tongue. Scanning electron microscopy of human foliate papillae and transmission electron microscopy of their resident taste buds was reported by Svejda and Janota (1974) and Azzali et al. (1996). The number of taste buds in human foliate papillae was reported by Hou-Jensen (1933) and Mochizuki (1939) (see Table 29.1). Confusion in finding taste buds within the folds of human foliate papillae reflects papilla structure. As many as 20 parallel ridges and furrows are found on the posterolateral margin of the human tongue. The rostralmost furrows (lateral rugae) contain no glandular ducts or taste buds, and their epithelia are more cornified than that between foliate papillae (Hou-Jensen, 1933). Fungiform papillae can be found on the tops of these lateral rugae. Although human foliate papillae were thought to be “rudiments” (in comparison to the well developed rabbit foliate papillae), Mochizuki (1939) calculated an average of 1300 taste buds per tongue, which exceeds the number of fungiform taste buds [800 buds: Braus, 1940; <1000 buds: Miller and Bartoshuk, 1991]. Indeed, contiguous taste buds within the same cleft may form a more functional unit, since they share access to a common taste stimulus pool. Foliate papillae are innervated by branches of the glossopharyngeal nerve (CN IX), but the more anterior portion also receives nerve fibers from the chorda tympani (Oakley, 1970; Pritchard, 1991).
29.2.2.4 Fungiform Papillae. Due to their morphological heterogeneity, fungiform papillae have been variously described as papillae clavatae, capitatae, lenticulares, obtusae, majores, and mediae (Haller, 1766; Sömmering, 1806). These papillae can be easily identified
Table 29.1 Distribution of taste bud numbers within the oral cavity of adult humans. Vallate Papillae – 400 252±151* 234±114* 240±125*
Fungiform Papillae
Foliate Papillae
Palate
20–30
?
15–20
<1000 (total) 800 (total)
Larynx
1279 – 708–1328 >2500 (neonate)
585 1120 *per papilla.
<25 (senile)
Author Hoffmann, 1875 Wyss, 1870 Arey, Tremaine, and Monzingo, 1935 Mochizuki, 1939 Miller and Bartoshuk, 1991 Braus, 1940 Hou-Jensen, 1933 Lalonde and Eglitis, 1961 Jowett and Shrestha, 1998 Cheng and Robinson, 1991 Miller and Reedy, 1990b
29.4 Salivary Glands of the Tongue
as pink elevations about 0.5 mm in diameter on the anterior portion of the living human tongue. Notwithstanding its convenient location, the fungiform taste bud population has been difficult to quantify since fungiform papillae vary in appearance and are distributed over a large area of tongue surface. The anterior portion of the tongue extends from the line of vallate papillae to the tongue tip (Figures 29.4 and 29.12). This region contains about 30 cm2 of surface area, depending on the size of the person, and the fungiform papillae are spread unevenly over it. The number of taste buds differs among fungiform papillae, and there are large variations among human subjects in fungiform taste bud distribution. Most papillae on the 5 mm margin of the tongue tip are shorter than those on more posterior regions. Following the surface in a posterior direction from the midline of the tip toward the back of the tongue, fungiform papillae become progressively larger in size, being largest in the more posterior lingual regions. Small, rounded papillae are present on the margin. Some of them contain taste buds, while others are comparable in size to filiform papillae but lack fila. Some papillae on the margin of the tip are elongated like conical papillae, and these, generally, lack taste buds. Fungiform papillae vary in size and shape: some are short and cuboidal, and others are tall with expanded heads like mushrooms. Among papillae on the margin of shorter height and smaller diameter (<0.5 mm), the distinction between filiform and fungiform papillae becomes obscure. Fungiform papillae occasionally have projections on their apices like small fila on filiform papillae. Taste buds have been quantified in terms of tongue surface areas, referred to as “taste bud density,” or number of taste buds per cm2 of tongue surface. There are about 145 gustatory (fungiform) papillae per lateral half of the tongue, with about 30 papillae per cm2 on the tip, but only about 3 papillae per cm2 on the posterolateral area. There are about 30 large fungiform papillae in the posteromedial region, for an estimated total of about 320 fungiform papillae per tongue (Miller and Reedy, 1990b; Shahbake et al., 2005). On 320 fungiform (gustatory) papillae, an average of about 3.5 taste buds per papilla has been estimated, for a total of 1120 fungiform taste buds (Miller and Reedy, 1990a, 1990b) (Table 29.1). Most investigators who study human fungiform papillae report the existence of papillae without taste buds, which rarely occurs in other mammals (Mistretta and Baum, 1984). Studies in humans show, depending on the methods used, that fungiform papillae lacking taste pores comprise 1–67% of the fungiform population per subject (Arvidson and Friberg, 1980; Cheng and Robinson, 1991; Miller and Reedy, 1990a; Segovia et al., 2002). This wide range may reflect how investigators decide which papillae are “fungiform.” Children possess a higher density of fungiform papillae, which correlates well with
643
increased sensitivity for sucrose (Segovia et al., 2002). Modern non-invasive imaging techniques, for example, confocal laser microscopy, allow the in vivo visualization of fungiform taste buds and their dynamics over a certain period of time, even buds that have not yet presented a taste pore (approx. 10%; Just et al., 2005; Srur et al., 2010) (Figure 29.8).
29.3 EXTRALINGUAL TASTE BUDS There are “extralingual” taste buds in regions of the oral, pharyngeal, and laryngeal cavities. Interestingly, Magendie (1820) and Carus (1849) erroneously associated the teeth with taste perception. Verson (1868) described the first “goblet-like organs” within the dorsal epithelium of the epiglottis, and Davis (1877) and Wilson (1905) observed taste buds in and the elicitation of taste perception from the human larynx. Lalonde and Eglitis (1961) counted more than 2,500 taste buds on the epiglottis, soft palate, laryngeal pharynx, and oral pharynx of one human neonate. Taste buds are evident in the epiglottis of one neonatal specimen (Rabl, 1895), and esophagus in human fetuses (Ponzo, 1907) and adults (Burkl, 1954; Schinkele, 1942). Taste buds are also found near the openings of sublingual salivary gland ducts in some other primates (Hofer et al., 1979), and near the ducts of the molar glands in rodents (Iida et al., 1983). In chickens and quail, taste buds in nonlingual parts of the oral cavity are almost always associated with salivary gland ducts (Ganchrow and Ganchrow, 1987). Miller and Smith (1984) estimate that about 25% of the hamster’s total taste buds are extralingual, and Mistretta and Baum (1984) accounted for a similar proportion of extralingual taste buds in the rat. It is not known whether extralingual taste buds are functionally different from those on the tongue. Taste buds of the epiglottis and/or uvula could be involved in initiation of upper airway reflexes (Bradley et al., 1983) and in the pharyngolaryngeal water response, possibly mediated by receptors signaling the absence of chloride ions (reviewed by Lindemann, 1996). Similarly, taste buds of the larynx seem not to play a role in gustation but detect chemicals that are not saline-like in composition, for example, CO2 (Bradley, 2000; Nishijima and Atoji, 2004). Apparently, structure and immunohistochemical properties of taste buds are remarkably conserved despite their different locations and innervation patterns (Kinnamon, 2011).
29.4 SALIVARY GLANDS OF THE TONGUE Lingua sicca non gustat (A dry tongue does not taste). This declaration of Haller (1766) refers to the dependence of
644
Chapter 29
Anatomy of the Tongue and Taste Buds
taste ability on solutions, within which tastants are dissolved and transported to the taste bud. Extralingual saliva is secreted by small, mostly mucous glands embedded in the epithelium of the cheek and palate. More saliva is produced by the serous parotid gland and the muco-serous sublingual and submandibular glands (Figure 29.3), whose secretory ducts open at the tongue frenulum just underneath its tip. Intralingual saliva originates from the mucoserous anterior lingual glands [glands of Blandin and Nuhn, (Tandler et al., 1994), Figure 29.3], and deep posterior serous salivary glands (Ebner) located in the submucous connective tissue below the foliate and vallate papillae of the tongue (Ebner, 1873; Riva et al., 1999). Their excretory ducts lead to the deepest sites of the papillar furrows (Figure 29.6). The gland lobules lie deeply in large patches of connective tissue which, in turn, are separated from each other by muscle fiber bundles. In addition, adjacent to Ebner glands in vallate papillae lie mucous (Weber’s) glands (Nagato et al., 1997), which in humans open into the crypts of the lingual tonsils (Zimmermann, 1927). Neither Weber’s nor Blandin-Nuhn glands lie in close proximity to taste buds and their particular significance for taste perception is unknown because of the difficulties in collecting saliva from these glands (Tandler et al., 1994). There is biochemical and histochemical evidence that the saliva of Ebner’s glands, as well as that of other non-lingual salivary glands, has more functions than that of a serious “washing solution.” Binding proteins such as Ebnerin (Li and Snyder, 1995) are supposed to modulate sensations. Schmale et al. (1990) isolated a protein from rat Ebner’s glands that is structurally similar to odorant binding proteins in Bowman’s glands of the olfactory mucosa. The gland is under autonomic control (Fukami and Bradley, 2005; Gurkan and Bradley, 1987). Interestingly, a recent report seems to point at a dependency of the hypoglossal nerve on sympathetic innervation of posterior lingual glands in hamsters (Cheng et al., 2009). For reports on specific ligand-receptor interaction with taste qualities, see Azen et al. (1990), Schmale et al. (1993), Spielman, (1990), Toto et al. (1993), and Chapter 31 of this volume.
29.5 BLOOD SUPPLY TO GUSTATORY PAPILLAE The mammalian tongue receives its blood supply from the lingual artery, which is usually a branch of the external carotid artery (Figures 29.3 and 29.4). Study of the tongue’s vascular system historically parallels that of the lingual papillae. For example, Albinus (1754), Sömmering (1806) (Figure 29.4) and Arnold (1839) performed intravascular injections in order to visualize the papillary surface. More recently, distribution of the blood supply
to different regions of the tongue and different types of lingual papillae has been described by Hellekant (1976). Each type of gustatory papillae is supplied by a characteristic capillary configuration (rat: Ohshima et al., 1990; cat, rabbit: Ojima et al., 1997a-c) and fine capillary networks are found adjacent to taste buds. The capillary loops of larger papillae in rats and dogs often show a constriction, maybe sphincter-like structures, but rarely arteriovenous anastomoses (Hu et al., 1996; Selliseth and Selvig, 1993). Taste stimuli injected systemically elicit responses in gustatory nerves as the bolus passes through the tongue (Bradley, 1973).
29.6 SOLITARY CHEMOSENSORY CELLS In addition to taste buds and free nerve endings, the solitary chemosensory cells (SCC) comprise another chemosensory system in vertebrates. They are not assembled in clusters, but are dispersed across the surface of the animal. SCC are related to taste bud cells in the sense that the former are secondary sensory cells with a slender, bipolar phenotype (Finger, 1997). “Classical” SCC have been studied first in teleosts (Whitear, 1992). The evolutionary benefits of these cells are still in question: In sea robins (Trigon), they are, beside taste buds, involved in finding food; in rocklings (Gaidropsarus) they are assumed to be important for predator avoidance (Kotrschal, 1996). Since the arginine-like receptor in catfish taste buds also occurs in SCC, Finger (1997) suggests that taste buds might include SCC within them. During development of fish, SCC seem to precede the development of taste buds. In mammals, however, SCC-like cells have been observed only transiently, during development. In newborn rats, single gustducin-immunopositive cells are seen in locations where later-developing vallate papillae will appear (Sbarbati et al., 1999). Individual slender cells, immunopositive for cytokeratin 20 (Witt and Kasper, 1999), an intermediate filament protein that is exclusively present in taste bud and epidermal Merkel cells (Moll, 1993; Zhang and Oakley, 1996; Zhang et al., 1995), are seen occasionally during early ontogenesis of the human tongue. Gustatory epithelia sensu strictu of adult mammals have not yet been reported to possess SCC. However, alpha-gustducin-immunoreactive SCC occur in the nasal mucosa of mice and have been interpreted as sentinels in the anterior nasal air passages (Finger et al., 2003). Taste receptors (Tas1R, Tas2R) in SCC along with their synaptic connectivity to CGRP-positive polymodal pain fibers of the trigeminal nerve indicate a role in detection of irritants and foreign substances by triggering trigeminally-mediated reflexes (Tizzano et al., 2011).
645
29.7 Cell Types of Vertebrate Taste Buds
29.7 CELL TYPES OF VERTEBRATE TASTE BUDS
29.7.1 Taste Buds of Lower Vertebrates – Cell Types
Peripheral taste organs differ in number, size, and shape in different vertebrate taxa, according to their importance for the particular species. For the sake of brevity, the following overview is restricted to some functionally well-characterized vertebrate species. Details are available in reviews by Reutter and Witt (1993) or Chaudhari and Roper (2010). Figure 29.9 shows a scheme representing the organization of cells in fish, frog, and mammalian taste buds.
29.7.1.1 Fish. In fish, and especially in some teleosts that are well-adapted to the dark, the taste organ is significantly more important for food intake than in amphibians and mammals. Thus, these fish, like the Siluridae, possess many more taste buds than representatives of the latter classes (Atema, 1971; Finger et al., 1996; Miller and Bartoshuk, 1991). The fish taste bud is generally pear-shaped and similar to that of mammals (Figure 29.9). Electron microscopic studies of teleost taste buds have
D
D
∗
L M
D L
III Sm D
w
Sr
I
II
w
H
Teleost (a)
Frog (b)
Rabbit (c)
Figure 29.9 (a)–(c) Longitudinal sections of taste organs from representatives of three different vertebrate classes. (a) Fish (bullhead, Teleostei), (b) Amphibian (frog, Anura), (c) Mammal (rabbit). In the schematic drawing, each sensory epithelial cell type is represented once with a distinct grey-step. The organs lie in squamous epithelium of different height, on top of dermal papillae which are also of different height. Each dermal papilla contains nerve fibers and a capillary vessel. (Below) 3D reconstructions of the respective apical taste bud portions. In all species, glia-like cells (blue in teleost and rabbit; sepia in frog “wing” cells) enwrap sensory cells. Sensory cells (green; sepia in rabbit as type II receptor cell). Nerve fibers entangle all cells, but synapses are seen only with type III cells in rabbit and microvillar (Sm) and rod-like receptor cells (Sr) in frog. (See plate section for color version.)
646
Chapter 29
Anatomy of the Tongue and Taste Buds
attempted, somewhat incompletely, to relate the ultrastructure and functions of taste bud cell types (for reviews see Jakubowski and Whitear, 1986; Reutter, 1986; Reutter and Witt, 1993). This is also apparent in the nonuniform usage of nomenclatures. Most authors refer to elongated “light” and “dark” taste bud cells, as well as “intermediate” and “degenerative” cells (Connes et al., 1988; Desgranges, 1965; Reutter, 1971, 1978; Welsch and Storch, 1969; Whitear, 1970). Generally, light cells are supposed to be “sensory” (receptor) cells, while the dark cells are regarded as “supporting” or “sustentacular” cells (e.g., Desgranges, 1965; Hirata, 1966; Whitear, 1970). However, Reutter (1992) considers the dark cells also as sensory because they exhibit synaptic contacts with nerve profiles or with basal cells. These observations, however, are not supported by the work of Grover Johnson and Farbman (1976) and Jakubowski and Whitear (1986). According to these authors the differentiation “light” and “dark” in combination with functional terms such as “supporting cells” and “sensory (receptor) cells” are misleading and should be avoided. According to Hirata (1966), Merkel (1880) and Reutter (1973) the taste bud may also have mechanoreceptive functions, particularly in view of the morphology of basal cells (Reutter, 1971, 1986) or serotonergic Merkel-like cells (Zachar and Jonz, 2011). While the existence of synaptic contacts of light and dark taste bud cells has not yet been finally proven, the different lengths of their microvilli perhaps suggest functional differences: The light taste bud cells have a single long microvillus reaching far into the mucous layer of the taste bud surface, the receptor area. By penetrating this layer, longer microvilli may be exposed to quite different “perireceptor events” (Getchell et al., 1984) than the small microvilli of dark taste bud cells that do not penetrate the mucous layer (Reutter, 1980; Witt and Reutter, 1990). In larvae of lampreys, representatives of fish-like jawless vertebrates (Petromyzontidae), taste bud cells were characterized by Retzius (1893) using the Golgi silver impregnation technique. Recently, Barreiro-Iglesias et al. (2010) reported three different cell types including serotonergic bi-ciliated cells, basal cells, and sustentacular cells. Ultrastructural (Reutter and Witt, 1993) and neurochemical (Ferrando et al., 2012) investigations in non-teleostean fish reveal clearly that taste buds differ within the main vertebrate taxa, which is partly represented in the differential expression of G protein-coupled receptors (Oka and Korsching, 2011). Further, in different systematic groups of fish the taste buds do not follow only one structural design. Thus, taxon-specific taste buds or cell types do not exist. Similar differences among mammalian taste buds point to a similar inevitable conclusion regarding particular phenotypes: There are only speciesspecific taste bud types, and a general “model” seems
difficult to find among vertebrates. This underlines the thesis that morphological phenotypes and the structural organization of taste bud cells do not necessarily reveal a general bauplan, but rather, reflect specific environmental conditions and/or feeding behaviors (Reutter and Witt, 1999). The influence of environmental differences has been studied in two closely related teleosts, one of which is sighted (Astynax mexicanus) and the other of which is a blind cave fish (Astynax jordani). Whereas taste bud morphology is rather similar, the cave fish compensates for blindness by significantly more gustatory axon profiles (Boudriot and Reutter, 2001) and an expanded expression of Prox 1 gene in developing taste buds (Jeffery et al., 2000; Varatharasan et al., 2009).
29.7.1.2 Amphibians. The taste organs of postmetamorphotic Salientia (=Anura), unlike piscine and mammalian taste bud bulb-like formations, are relatively large disk-like epithelial differentiations of the dorsal lingual and palatal mucosa (Figure 29.9). Waller (1847, 1849) and Engelmann (1872) called these structures “Geschmacksscheibe” or “taste disc.” In contrast to Salientia, the taste buds of the urodeles [= Caudata, e.g., mudpuppy (Necturus), newt (Triturus) or Axolotl (Ambystoma)] have a bulb-like shape (Cummings et al., 1987; Delay and Roper, 1988; Fährmann, 1967; Farbman and Yonkers, 1971; Toyoshima et al., 1987; Toyoshima and Shimamura, 1987). The cellular elements of the taste disc, or “Endscheibe” (Merkel, 1880), of the frog were subject to numerous investigations and received various designations: After Waller (1847, 1849) had first distinguished between papillae conicae (=P. filiformes) and papillae fungiformes, Fixsen (1857) described two different cell types, the so-called “cellulae cylindricae” and “cellulae fusiformes,” the processes of which pass through the whole sensory epithelium to reach the connective tissue core of the papilla. Engelmann (1872) and Merkel (1880) further developed the terminology: Merkel distinguished between “cylindrical cells” (Cylinderzellen) situated on the epithelial surface and surrounding “wing cells” (Flügelzellen), the nuclei of which lie deeper in the epithelium. After Graziadei and DeHan (1971) had described only two cell types (“associate cells” and “sensory cells”) in electron microscopy, the close relationship between “rod cells” (Stäbchenzellen) and cylindrical cells (Merkel, 1880) was recently re-introduced by von Düring and Andres (1976). In addition, the latter authors first described basal cells and Merkel cells of the frog taste disc, which are the only cells that do not contact the epithelial surface. The taste disc in adult frogs contains up to eight cell types (Reutter and Witt, 1993): mucus cells, wing cells, two types of sensory cells (cylindrical and rod-like type), two types of basal cells [stem and
29.7 Cell Types of Vertebrate Taste Buds
Merkel cell-like basal cells (Zancanaro et al., 1995)], and marginal cells and ciliated cells (Toyoshima et al., 1999) (Figure 29.9). The cell types and the history of the nomenclature are described in detail by Jaeger and Hillman (1976), Reutter and Witt (1993), Witt (1993), Osculati and Sbarbati (1995), and Li and Lindemann (2003). Tadpoles possess so-called premetamorphic papillae which bear bud-like taste organs at their tops. During metamorphosis, these structures wholly disappear and are replaced by fungiform papillae with large taste ˙ ˙ disks (Nomura et al., 1979; Zuwała, 1997; Zuwała and Jakubowski, 1991). Tadpole taste discs consist of sensory and supporting cells, and basal cells are lacking. Taste buds of the mudpuppy (Necturus, Urodela) are similar to those of fishes. They are composed of dark and light cells and possess serotonergic Merkel cell-like basal cells which are synaptically connected with either nerve fibers or dark and light cells (Delay et al., 1994, 1993; Delay and Roper, 1988).
29.7.1.3 Reptiles and Birds. Lingual taste buds in reptiles have been described in turtles (Iwasaki et al., 1996; Korte, 1979), tortoises (Pevzner and Tikhonova, 1980), and some lizards (Uchida, 1980). Lizards (Gekkonidae or Anguidae), as well as snakes, have virtually no taste buds on the tongue, but rather on the buccal floor and oral epithelia of the mandible and maxilla (Toubeau et al., 1994). In shape, reptilian taste buds resemble those of mammals. There are up to five different types of taste bud cells, classified into light and dark cells and as types 1,2,3,A,B, or as types I, II, II, and basal cells (Reutter and Witt, 1993). Reptiles and birds belong to the same superclass, and one might expect a similar organization of avian taste buds. However, the few examples of bird taste buds show great variability among species. Buds in grain-eating birds appear in the posterior part of the tongue, near the pharynx, and in the distal palatal mucosa (Ganchrow et al., 1991; Ganchrow and Ganchrow, 1987; Saito, 1966; Sprissler, 1994). Unlike mammals, avian taste buds do not reside within lingual bud-bearing papillae. In addition, taste buds contain tubular-like channels circumscribed by elongated cells grouped in a rosette configuration, with the channel lumen continuous apically with the taste pore (Berkhoudt, 1985; Ganchrow et al., 1993). Taste buds in chicken are richly innervated (Ganchrow et al., 1986), contain gustducin in a subset of taste cells (Kudo et al., 2010), and synapses are seen between all cell types (light cells and dark cells) and nerve fibers (Reutter and Witt, 1993; Sprissler, 1994). Stornelli et al. (2000) observed four cell types in duck taste buds: light cells, dark cells, intermediate cells, and basal cells.
647
29.7.2 Mammalian Taste Buds – Cell Types Early histological investigators of mammalian taste buds described two types of elongated, fusiform cells in taste buds of human vallate papillae (Schwalbe, 1868): “supporting” and “taste cells,” the latter divided into Stiftchenzellen (pin cells) and Stabzellen (rod cells) with differences in contrast and brightness (Figure 29.5). Classification into “light” and “dark” taste bud cells was also used in early electron microscopic analyses (Engström and Rytzner, 1956). Farbman (1965) considered dark, fusiform taste bud cells of human fungiform papillae as sensory cells (type I), whereas other investigators such as Paran et al. (1975) described a type II-cell that contains numerous vacuoles and mitochondria, especially in apical areas. This latter cell is not believed to be sensory. Cottler Fox et al. (1987) speculated that the different electron densities are due to irreproducible fixation artifacts. In general, ultrastructural and immunohistochemical criteria are considered more important for the classification of cells than the evaluation of the electron density of the cytoplasm. Moreover, present understanding in mammalian taste bud cytology leads to using a rather heterogeneous nomenclature, based on morphological and functional differences across species. The basis for the current nomenclature was established by the Murrays and colleagues (Murray, 1986; Murray and Murray, 1967, 1971; Murray et al., 1969) in taste bud cells of the rabbit foliate papillae. However, these cell types differ in some respects from rodent taste buds (Kinnamon et al., 1985, 1993, 1994; Pumplin and Getschman, 2000; Pumplin et al., 1997, 1999). Thus, Royer and Kinnamon (1988) observed considerable deviations in the cytoarchitecture of murine foliate taste buds compared to that of other mammals. For example, they did not find type III cells, and all bud cells had synaptic connections with nerve fibers. Most current information on chemoreception of taste stimuli and information transfer to primary afferent axons have been established in mice (Dando and Roper, 2009; Huang et al., 2009; Roper, 2006), but there are significant species differences (Ma et al., 2007), and the precise organization of the taste bud in humans remains to be determined (Azzali, 1996, 1997; Paran et al., 1975; Witt and Reutter, 1996). An example for a more generalized taste bud is depicted in Figure 29.10. Work of the last two decades has revealed that taste stimuli are received by type II receptor cells (Tomchik et al., 2007), while type III (presynaptic) taste cells are the only ones that contain synaptic proteins and form synapses with nerve fibers (Kinnamon et al., 1988). The information transfer from type II (receptor) cells to type III (presynaptic) cells is mediated through ATP and pannexin hemichannels (reviewed by Chaudhari and Roper, 2010) or directly
648
Chapter 29
I
Anatomy of the Tongue and Taste Buds
III
II
V
IV
Figure 29.10 Mammalian taste bud in longitudinal section, idealized schematic drawing according to electron microscopical findings. Each cell type is depicted once. Following Murray‘s nomenclature, cells of type I, II and III are elongated and form the buds sensory epithelium proper. Apically, these cells end with different types of microvilli within the taste pit and may reach the taste pore. Type I cells are glia-like, type II cells comprise receptor cells for bitter, sweet, and umami stimuli. Synapses are only found at the bases of type III (presynaptic) cells. Type IV cells are basal cells, type V marginal cells. Nerve fibers within the short dermal papilla are slightly myelinated, and within the taste bud they form an unmyelinated plexus. Note the basal lamina between dermis (which contains a capillary) and the epithelium.
from type II cells to nerve fibers, as gustatory afferents also contain purinergic receptors P2X2 and P2X3 for the interaction with ATP (Finger et al., 2005). A survey representing the most important substrates associated with taste cell types in vertebrates is shown in Table 29.2.
29.7.2.1 Type I Cells (Glia-Like Cells). These cells are the most frequent. They are spindle-shaped and have a basal process that envelops the axons in a Schwann cell-like manner. Type I cells protrude with brush-like, long microvilli (1–2 μm) into the taste pit. These cells ensheath type II and type III cells with cellular protrusions and may insulate them (Figures 29.9 and 29.10). Apically, they contain large granules, 100–400 nm in diameter (Murray,
1986). The nuclei of type I cells are irregularly shaped. According to Murray and Murray (1971) and Murray (1986) these cells have a secretory (supporting cells) and possibly phagocytotic function, and probably produce the amorphous material of the taste pit (e.g., (Farbman, 1965; Menco, 1989; Ohmura et al., 1989; Witt, 1996). Type I cells are involved in neurotransmitter clearance and ion redistribution, similar to the function of glia cells in the central nervous system. They contain GLAST, a glutamate transporter (Lawton et al., 2000), as well as enzymes degrading extracellular ATP (Bartel et al., 2006). Some type I cells possess the K+ channel ROMK that may eliminate accumulated extracellular potassium ions to retain the excitability of type II and type III cells (Dvoryanchikov et al., 2009).
29.7.2.2 Type II Cells (Receptor Cells). Most of these cells are located in the periphery of the taste bud. They are fusiform, but do not possess enveloping processes, or granules. Their cytoplasm is moderately electron-dense, and nuclei are round to oval. Synapses are not observed (Farbman et al., 1985, 1987). Toyoshima and Tandler (1987) describe a modified endoplasmic reticulum with specialized sub-surface cisterns adjacent nerve profiles. In mice, vallate and foliate “light” (type II-) and “dark” (type I- and type II-) taste bud cells exhibit synaptic contacts with nerve fibers, thus suggesting a gustatory function. However, type I- and type II- cells do not form synapses with the same nerve fibers (Kinnamon et al., 1985, 1988; Royer and Kinnamon, 1988). These cells are equipped with G-protein coupled receptors and tuned to sweet, bitter, and umami, but not to sour and salty taste (Matsunami et al., 2000; Tomchik et al., 2007). 29.7.2.3 Type III Cells (Presynaptic Cells).
Taste buds contain only 5–7% of type III cells. They have unbranched basal and apical processes. Their apical portion protrudes with a single large microvillus into the taste pit and may reach the taste pore. Type III cells are the only cells that have synaptic contacts with intragemmal nerve fibers. Near the cell nucleus there are numerous dense-cored vesicles (80–140 nm in diameter) which are involved in neurotransmitter synthesis (GABA, serotonin, norepinephrine) (Fujimoto et al., 1987; Hokfelt et al., 1980; Huang et al., 2005; Nada and Hirata, 1977). Type III cells contain several synaptic proteins and are therefore termed “presynaptic cells” (DeFazio et al., 2006). Their apical process apparently possesses channels for sour taste reception (Huang et al., 2008).
29.7.2.4 Type IV Cells (Basal Cells). Type IV cells (Murray, 1973; Murray et al., 1969) include basal cells (Nemetschek-Ganssler and Ferner, 1964) or “pregustatory cells” (Scalzi, 1967). These are relatively small
649
29.7 Cell Types of Vertebrate Taste Buds
Table 29.2 Survey of selected substances (transmitters, channel or transporter proteins) associated with certain types of taste bud cells in various species. Taste Bud Cell Type Basal Cells basal cells basal cells I I I I II II II
II II II II n.d. II
II II II II II II II II II (III?) II (Gustducin-neg.) (II) (III) III II (II) II (Gustducin neg.) III III III
III III III III III (5HT-neg.)
Substance/Transmitter
Species
Reference
5HT (serotonin) 5Ht, Glu, GABA 5HT Glutamate/aspartate transporter (GLAST) Ecto-ATPases Epithelial Na+ channel (ENAC)
catfish necturus frog mouse
Reutter, 1971 Kim and Roper, 1995; Nagai et al., 1996 Jain and Roper, 1991 Lawton et al., 2000
mouse mouse
K+ channel ROMK 5HT, Serotonin transporter Acetylcholine Acetylcholine transporter, Choline-acetyltransferase (ChAT), Vasoactive intestinal peptide (VIP) Cholecystokinin Neuropeptide Y Type III IP3 receptor Gustducin Gustducin
mouse rat mouse mouse
Bartel et al., 2006 Lin and Kinnamon, 1999; Vandenbeuch, Clapp, and Kinnamon, 2008 Dvoryanchikov et al., 2009 Ren et al., 1999 Dando and Roper, 2009 Ogura et al., 2007
rat, carp
Shen et al., 2005; Witt, 1995
rat rat rat, mouse chicken mouse, rat, hamster
Herness et al., 2002 Zhao et al., 2005 Clapp et al., 2001 Kudo et al., 2010 Boughter Jr. et al., 1997; Hoon et al., 1995; McLaughlin, McKinnon, and Margolskee, 1992; Ruiz-Avila et al., 1995 Behrens et al., 2012 Yee, Bartel, and Finger, 2005 Clapp et al., 2004 Behrens et al., 2012 Perez et al., 2002 Matsunami, Montmayeur, and Buck, 2000 Hoon et al., 1999 DeFazio et al., 2006
TAS2R38 (bitter taste receptor) NGF, trkA PLCbeta2 PLCbeta2 TRPM5 T2R T1R GPCRs signal molecules for bitter, sweet and umami ATP release PGP 9.5 Snap 25
human mouse Mouse Human mouse
Snap 25 SNAP25, synapsin II, NCAM,AADC. GABA, glutamate decarboxylase (GAD) GABA GABAB2 GAD, GABA-B Receptor GAD 5HT
rat mouse
Bartel et al., 2006; Finger et al., 2005 Yee et al., 2001 Oike, Matsumoto, and Abe, 2006; Pumplin and Getschman, 2000; Ueda et al., 2006 Yang et al., 2000 DeFazio et al., 2006
rat
Cao et al., 2009
rat mouse mouse mouse mouse, rat, rabbit, monkey
Obata et al., 1997 Starostik et al., 2010 Starostik et al., 2010 DeFazio et al., 2006 Fujimoto, Ueda, and Kagawa, 1987; Kaya et al., 2004; Nada and Hirata, 1975; Nada and Hirata, 1977 Huang et al., 2005 Fujimoto, Ueda, and Kagawa, 1987 Nelson and Finger, 1993 Yee, Bartel, and Finger, 2005 Yee et al., 2001
5HT 5HT NCAM BDNF, trkB Protein gene product 9.5 (PGP 9.5)
mouse mouse rat rat
mouse monkey, rb rat mouse rat
650
Chapter 29
Anatomy of the Tongue and Taste Buds
undifferentiated cells that lie at the taste bud’s base, which do not form processes that reach the pore. They contain numerous bundles of intermediate filaments (Royer and Kinnamon, 1991), and differ from Merkel cell-like basal cells of fishes and amphibians. Type IV cells are considered to be undifferentiated stem cells of their bud cell progeny (Chaudhari and Roper, 2010; Murray, 1973; Murray, 1986; Roper, 1989). In embryonic and adult vallate taste buds of mice, basal cells also express the transcription factors Hes6 and Mash-1, the latter possibly being involved in specification of a type III lineage (Seta et al., 2003, 2011). Using genetic lineage tracing in murine taste buds, Miura et al. (2014) found sonic hedgehog (shh) in most basal cells, which indicates a fate as postmitotic, immediate precursors of all three cell types rather than a stem cell. Some authors report on “intermediate cells” (e.g., Kinnamon et al., 1985). It has been pointed out (Farbman et al., 1985; Roper, 1989) that differences in the electron density of the cytoplasm could also reflect different stages in the maturation of the same cell type which indicate different states of function.
29.7.2.5 Type V- Cells (Marginal Cells).
“Marginal cells” (also “perigemmal cells,” and, in extension of Murray’s nomenclature, “type V cells”) have been described (Beidler and Smallman, 1965; Farbman, 1980; Gurkan and Bradley, 1987; Reutter and Witt, 1993). However, they have nothing in common with the secretory marginal cells of taste organs in fish and frog, and may possibly be taste bud stem cells (Beidler and Smallman, 1965; Farbman, 1980) which express particular non-taste receptor proteins, for example, CD44 isoforms (Witt and Kasper, 1998) during human taste bud ontogenesis.
29.7.3 Molecular Markers of Taste Bud Cells One of the most intriguing challenges for suggesting possible functional properties of taste bud cells is to identify subsets of these cells by morphological features as well as molecular properties, many of which can be traced even in enriched primary taste bud cell cultures (Kishi et al., 2001, 2002; Ozdener et al., 2006). Histochemical evidence on the neurochemical nature of taste cells have identified the panneuronal markers, neuron-specific enolase (NSE) and protein gene product 9.5 (PGP 9.5) (Astbäck et al., 1997; Montavon et al., 1996; Yee et al., 2001; Yoshie et al., 1988), carbohydrate- binding proteins, the lectins (Witt and Miller, 1992; Witt and Reutter, 1988). Immunoelectron microscopic studies have tried to match functional parameters with those of conventional electron density. For example, cell adhesion molecules (Nolte and Martini, 1992; Smith et al., 1993, 1994) and several blood-group
antigens (Pumplin et al., 1997, 1999; Smith et al., 1999) characterize subsets of type II taste bud cells. A subset of the (light) type II cell contains partly the G protein gustducin (Menco et al., 1997; Ruiz-Avila et al., 1995), which is involved in the perception of sweet and bitter taste (Tomonari et al., 2012; Wong et al., 1996). Choline acetyl transferase, an enzyme involved in the synthesis of the neurotransmitter acetylcholine, has been identified in rat type II cells (Menco et al., 1997). Whereas the putative neurotransmitter serotonin is confined to basal cells of fish taste buds (Reutter, 1971) and Merkel cell-like basal cells of amphibian taste organs (Delay et al., 1997; Hamasaki et al., 1998; Toyoshima and Shimamura, 1987), serotonin in mammals has been described in type III cells in the rabbit (Fujimoto et al., 1987; Kim and Roper, 1995) and human taste buds (Azzali, 1997). This led to the hypothesis that these cell types were equivalent in both taxa (Kim and Roper, 1995). Lindemann (1996) suggests the term “serotonergic cells” instead of type III cells (<10% of all cells). Generally, neuropeptides are located in intragemmal nerve fibers rather than in particular bud cells. An exception is vasoactive intestinal peptide (VIP) that has been detected in a subset of rat type II cells (Herness, 1989; Shen et al., 2005), and in light taste bud cells in the carp (Witt, 1995) by electron microscopy. Though most of these markers are expressed only in differentiated cells and are not evident after nerve dissection (Smith et al., 1993; Whitehead et al., 1998), their functional correlation with taste perception data is mostly unknown. To avoid the present Babylonian confusion of tongues with regard to taste bud cell nomenclature, present research directions try to associate electrophysiologicallycharacterized, isolated taste bud cells with a particular cell type based on its specific substrate expression. Modern cell biological approaches, for example, introduction of green fluorescent protein chimeras in vitro (Landin et al., 2005) or calcium imaging after application of specific stimuli (Caicedo et al., 2000), have contributed to a solution of this problem. Several authors report on morphological and immunohistochemical differences between vallate/foliate and fungiform taste buds within the same species. For example, mouse taste bud cells of fungiform papillae contain more synapses and presynaptic vesicles than those of vallate papillae (Kinnamon et al., 1993), and the number of taste bud cells containing group H blood antigen and gustducin is three times higher in vallate than in fungiform papillae (Smith et al., 1993). The coexpression pattern of taste receptors (T2R and T3R) and gustducin differs between fungiform and vallate taste buds in mice (Kim et al., 2003). In rabbit, lectin carbohydrate profiles of both taste bud populations differ as well (Witt and Miller, 1992). The reasons and significance of these differences between fungiform and vallate/foliate taste cells are not clear, but
29.8 Development of the Human Peripheral Taste System
factors determining their varying phenotype could include a different local saliva composition (Schmale and Bamberger, 1997; Schmale et al., 1990; Shatzman and Henkin, 1981) or morphogenetic conditions of local epithelium (Smith et al., 1999). Evidence for communication between taste cells, apart from purinergic transmission (Finger et al., 2005), includes the presence of cell adhesion molecules (Nolte and Martini, 1992; Smith et al., 1993), heparin-binding proteins (Wakisaka et al., 1998), and membrane receptors that influence the intracellular signal transduction cascades. For example, the hyaluronan receptor, CD44, was identified in a subset of human fetal taste bud cells (type V, marginal cells) and most of adult human taste bud cells (Witt and Kasper, 1998). This transmembrane protein is linked to a series of actin-associated microfilaments, for example, ezrin and ankyrin, which are located in microvilli of type I cells and might influence the function of ion-translocating membrane proteins (Höfer and Drenckhahn, 1999). In light of efferent neural control, taste bud cell communication may be mediated via local axon reflexes between sensory cells (Caicedo et al., 2000, Reutter and Witt, 2004).
29.8 DEVELOPMENT OF THE HUMAN PERIPHERAL TASTE SYSTEM Morphogenesis of the mouth cavity is characterized by the development of the tongue anlage which appears prior to, and is a prerequisite of, the formation of gustatory papillae. At the embryonic age of 4 weeks, the first structure of the tongue anlage to appear is the tuberculum impar which is situated between the first (mandibular) and second (hyoid) branchial arches (Figure 29.11). Then, anterolateral to the tuberculum impar, the paired lingual swellings (which derive from the medial parts of the mandibular arches) fuse with the tuberculum impar. The tongue’s base is formed by the hypobranchial eminence (copula of His) forming within the third and fourth branchial arches. The border between the caudal part and the body of the tongue is demarcated by a V-shaped rim, the sulcus terminalis (Bradley, 1972; Witt and Reutter, 1997). The innervation pattern of cranial nerves, which later supplies particular lingual regions, reflects the early innervation of branchial arches (see Figure 29.11): The pretrematic nerve of the first branchial arch is the lingual nerve (from CN V3 ); that of the second arch, the chorda tympani (from the intermedio-facial nerve); and that of the third arch constitutes later lingual rami of the glossopharyngeal nerve (for details see textbooks on embryology, for example, Hinrichsen, 1990; Williams et al., 1989). The first detailed developmental studies on the surface appearance of the tongue were carried out by Froriep
651
(1828), and continued histologically by Tuckerman (1889), Gråberg (1898), and Hellman (1922). Hermann (1885) described the stages of karyokinesis in developing taste buds. It was unclear to Hermann if supporting, or neuroepithelial, cells were being replaced. Vallate papillae start to develop earlier than fungiform papillae, and begin with the appearance of a central midline papilla just behind the foramen caecum around the sixth postovulatory week. From week 7 on, there develop many hillock-like epithelial elevations on the tongue’s dorsum, as seen with scanning electron microscopy (Figure 29.12). Some of these elevations are precursors of fungiform papillae and are especially densely distributed near the midline and the lateral ridges of the tongue (Habermehl, 1952; Hersch and Ganchrow, 1980; Witt and Reutter, 1997). Analysis of serial sections of the tongue encompassing this critical developmental age (weeks 6–8) demonstrates that not every dermal elevation will be the target of nerve fibers. First, around week 7–8, nerve fibers, migrating towards the periphery, form a large intragemmal plexus. Our own studies show that there are no taste bud anlagen without approaching nerve fibers (Witt and Reutter, 1996; Witt and Kasper, 1998), but recent studies revealed the nerve-independent development of taste buds and their preforming papillae (Barlow, 2003; Ito and Nosrat, 2009; Nosrat et al., 2012; Stone et al., 1995; Thirumangalathu et al., 2009). Also, taste bud primordia without dermal papillae are evident, as well as individual bipolar epithelial cells resembling solitary chemosensory cells. These individual cells are immunopositive for cytokeratin 20, a marker for lingual taste bud cells (Witt and Kasper, 1999; Zhang and Oakley, 1996). Temporal correlation, which would suggest dependence of taste bud development on nerve ingrowth, has not as yet been seen. Lingual taste bud primordia first occur around the 7th and 8th postovulatory weeks (Bradley, 1972; Bradley and Stern, 1967). Taste pores, commonly acknowledged as a sign of taste bud maturity, appear between the 10th and 14th week. The presence of a taste pore is not always associated with a fully mature taste bud because the bottoms of early taste pits may be covered by flat epithelial cells (Witt and Reutter, 1997). However, transmission electron microscopical studies show that early taste bud primordia (week 8) synaptically contact nerve fibers, suggesting the potential for neurotransmission precedes the exposure of sapid molecules to the apical surface of the taste bud cell. At its base, the developing human taste bud (weeks 12–15) contains processes of dark and light cells, as well as processes resembling type III cells (exhibiting synapses with nerve fibers). At their apical ends, taste bud cells cannot be distinguished by their electron density (week 15, Figure 29.13). There are cells with long, slender microvilli, but, in contrast to adult taste buds (Azzali, 1997), there are no type I cells
652
Chapter 29
Anatomy of the Tongue and Taste Buds
1
I
V3
2 3
II
4
III
VII
5
IX
IV X
XII
Figure 29.11 Development of the human tongue, 5th postovulatory week. The schematic drawing was done by compiling Hinrichsen‘s (1990) and our own data. – By horizontal section the floor of the forecoming buccal cavity of a human embryo is removed and viewed from dorsally. The floor relief is derived from the branchial arches I (mandibular arch), II (hyoidal arch), III (3rd pharyngeal arch) and IV (4th pharyngeal arch), and by their derivatives which are 1- the paired lingual swellings, 2- the impar tubercle and 4- the hypobranchial eminence. These three structures form the tongue anlage. Between 2 and 4, the anlage of the thyroid gland invaginates, and as its remnant the 3- foramen caecum is left. 5- is the anlage of the epiglottis. The branchial arches, as well as the tongue anlage, are innervated by the cranial nerves V3 (mandibular nerve), VII (facial nerve), IX (glossopharyngeal nerve) and X (vagal nerve). (CN XII -hypoglossal nerve- invades the tongue anlage as well, and innervates its muscular system). Later, the lingual nerve (from V3 ) and the chorda tympani (running with VII) join each other and to supply the anterior two- thirds of the tongue with somatosensory and gustatory nerve fibers, whereas IX and X carry taste fibers for the posterior third of the tongue, the epiglottis and the pharynx.
Figure 29.12 Scanning electron micrograph of a human embryonic tongue, 7th postovulatory week. Fine dots in the dorsal surface demarcate later fungiform papillae. Anlagen of vallate papillae (arrows) lie in front of the sulcus terminalis. Short arrow indicates the median vallate papillae, which originates first. Scale bar: 0.5 mm.
653
29.9 Innervation of the Human Tongue and Taste Buds
TP
N
∗ N
dC
BL
mC
BL
N
Figure 29.14 Basal portion of a developing human taste bud, week
mC
15 (detail from Figure 29.13). Numerous processes of an electron-dense cell (dC) rich in dense cored vesicles surround nerve fibers (N), but synapses and signs of release of the vesicular contents are not observed. One cell process is filled with dense-cored and clear vesicles (asterisk). BL = basal lamina. Bar = 1 μm. From Witt and Reutter (1996), with permission of John Wiley & Sons.
N
N
mC
N
N BL
Figure 29.13 Transmission electron micrograph of a human fungiform taste bud during development (week 15). The taste pore (TP) is already open, and some elongated cells stick into the taste pit. However, differences between cell types in the apical portion of the taste bud cannot be made yet. There is no mucus in the taste pit. Approximately two- thirds of the taste bud are filled with ramifications of nerve fibers (N). A part of the basal portion is outlined with a rectangle (see Figure 29.14). mC = marginal cell, BL = basal lamina; scale bar: 10 μm. From Witt and Reutter (1996), with permission of Wiley & Sons.
with typical dark granules believed to secrete the mucous material that fills the taste pit (Witt and Reutter, 1996).
29.9 INNERVATION OF THE HUMAN TONGUE AND TASTE BUDS The tongue is innervated by (1) motor nerve fibers constituting the hypoglossal nerve (CN XII), which supplies the inner (intrinsic) and the hyoidal tongue muscles; (2) somatosensory nerve fibers, composed of divisions of the trigeminal (CN V3 ) and glossopharnygeal (CN IX) nerves; (3) autonomic nerve fibers which stem from the intermedio-facial nerve (CN VII), the glossopharyngeal nerve, and the vagus nerve (CN X); and (4) sensory (gustatory) nerve fibers that transmit taste information centrally
from taste buds, namely (a) the chorda tympani, a branch of the intermediate nerve (generally considered a part of the facial nerve, CN VII), (b) the greater (=superficial) petrosal nerve, also part of the intermedio-facial complex, (c) glossopharyngeal nerve (CN IX), and (d) vagus nerve (CN X) (summarized in Figure 29.15). Classical research papers of the nineteenth century explored the clinical consequences in taste perception associated with diagnostic features of the cranial nerves. These papers have formed the bases for the neurological examination. Two prominent themes were explored: (1) Which cranial nerves are associated with functional attributes of the taste system? (2) How is taste perception affected by neurological diseases? In physiological experiments, Magendie (1820) dissected the lingual nerve of living, unanaesthetized animals and observed loss of taste, but intact movement and sensation of palate, gingival, and buccal mucosa. Panizza (1834) performed dissection of the glossopharyngeal nerve resulting in loss of taste. Alcock (1836) described the role of the chorda tympani and the sphenopalatine (pterygopalatine) ganglion. Lussana (1869, 1872) traced the target tissue of the chorda tympani nerve to the anterior two-thirds of the tongue. The dependence of taste buds on nerve supply was experimentally shown by von Vintschgau and Hönigschmied (1877): 40 days after dissection of the glossopharyngeal nerve, the number of taste buds dramatically decreased. In similar experiments, Ranvier (1888) observed that taste bud sensory cells degenerate, and supporting cells pushed through the pore to the tongue surface. During this process, he observed cellules migratrices [phagocytic fibroblasts? (Suzuki et al., 1996)] loaded with fed particles, which were “probably responsible for removal of old material.” Soon it became evident that experiments based on vivisection were not
654
Chapter 29
Anatomy of the Tongue and Taste Buds
V V1 V2
gG VII
V3
pG
IX LN
Figure 29.15 Innervation of the human tongue and the taste X XII
CT iG
iG
sG
only painful for the animal (mostly dogs or cats), but also unreliable in their results (Alcock, 1836; Wagner, 1837). Nevertheless, the overall conclusions derived from these nineteenth century nerve dissection experiments (reviewed by Jägel, 1991; Parker, 1922) cannot deny their import for current knowledge of cranial nerve supply and taste sensitivity. An elegant review of the background of peripheral taste pathways in humans was written by Lewis and Dandy (1930). They examined both the neurological and neuroanatomical literature on gustatory pathways. The sensory distribution of the facial nerve and its clinical importance was described by Hunt (1915). He disentangled the overlapping sensory fields of the facial nerve (including the chorda tympani) from the trigeminal nerve by documenting the distribution of herpes zoster inflammation. The herpetic eruptions outlined the sensory fields of the geniculate ganglion on the tongue, soft palate, and ear. Another basis for evaluating the involvement of the chorda tympani nerve with lingual taste buds came from patients who had undergone middle ear surgery (Borg et al., 1967; Bull, 1965). Contemporary reviews of human (Norgren, 1990; Prichard, 2011) and primate (Pritchard, 1991) taste pathways have incorporated observations from the second half of the twentieth century, particularly those derived from electrophysiological studies. 1. Chorda tympani and greater petrosal nerve: Distal to the intermediate nerve branch of the facial nerve, peripheral axons of some geniculate ganglion somata (the chorda tympani nerve) take a recurrent course within the facial canal in the petrosal part of the temporal bone, pass through the middle ear, and exit the skull via the petrotympanic fissure to join the lingual division of the trigeminal nerve, the lingual nerve.
bud-bearing epithelia (hatched regions), compiled from (Feneis, 1985) and (Sobotta, 1993). The cranial nerves VII (which includes the intermediate nerve with its branches, greater petrosal nerve and chorda tympani), IX and X contain sensory gustatory fibers (yellow). V, trigeminal nerve (blue) with its divisions V1 , ophthalmic, V2 , maxillary, and V3 , mandibular nerves. XII, hypoglossal nerve (red), is the motor nerve of the intrinsic tongue muscles. gG, geniculate ganglion; pG, pterygopalatine (sphenopalatine) ganglion; iG inferior ganglion of the glossopharyngeal (IX) and vagal (X) nerves, respectively; sG, submandibular ganglion with postganglionic autonomic nerve fibers of the chorda tympani to supply the submandibular and sublingual glands. (See plate section for color version.)
Both intermedio-facial (gustatory) and trigeminal (somatosensory) fibers run in the lingual nerve and distribute to the fungiform papillae on the anterior two thirds of the tongue and may reach also the anterior portion of the foliate papillae. Taste buds on the soft palate are innervated by the greater petrosal branch of the intermedio-facial nerve, whose somata also lie within the geniculate ganglion (Harris, 1952; Miller and Spangler, 1982). Some chorda tympani fibers are reported to anastomose with the greater petrosal nerve via the otic ganglion (Pritchard, 1991; Schwartz and Weddell, 1938). Both the greater petrosal and chorda tympani nerves also carry parasympathetic fibers to their associated salivary glands: The greater petrosal nerve serves the palatine and the lacrimal glands, while the chorda tympani innervates the submandibular and sublingual glands via the submandibular ganglion. 2. Glossopharyngeal nerve: Axons of the glossopharyngeal nerve originate from ganglion cells mainly in the inferior (petrosal) glossopharyngeal ganglion. These peripheral axons supply both taste buds and general sensory innervation to the vallate and foliate papillae. Salivary glands (Ebner) are supplied by parasympathetic fibers via an intrinsic ganglion (Remak, 1852). Probably, the glossopharyngeal nerve also supplies taste buds in the pharynx. Bourgery and Jacob (1839) and Doty et al. (2009) observed that some CN IX fibers extend into the middle part of the tongue to overlap with innervation areas of the chorda tympani. However, it is unclear if they innervate taste buds. 3. Vagus nerve: Taste buds on the laryngeal surface of the epiglottis, larynx, and proximal portion of the esophagus are innervated by the superior laryngeal
References
branch of the vagus nerve, which has the perikarya of its chemosensory neurons in the inferior (nodose) vagal ganglion. 4. Trigeminal nerve: The possible role of trigeminal nerve fibers in taste perception has been discussed for two millenia, and there is no end in sight. Via the lingual nerve, this nerve conveys somatosensory and viscerosensory information from the tongue to trigeminal brain stem nuclei. In fact, most of the nerve fibers entering the fungiform papillae are trigeminal, while a few fibers originate from the chorda tympani (25% in rat: Farbman and Hellekant, 1978). Trigeminal fibers may respond to sapid stimuli, as revealed by trigeminal transection experiments (Berridge and Fentress, 1985), electrophysiology (Harada and Smith, 1992), and trigeminal ganglion cell response (Liu and Simon, 1998). Taste receptors also occur in a variety of nongustatory cells proper, outside the oral cavity (Tizzano et al., 2011). Finally, taste qualities may be influenced by nonsapid stimuli, for example, temperature: approximately one-half of the nerve fibers involved in taste transduction respond to temperature (Cruz and Green, 2000). The interaction of both gustatory and somatosensory qualities may be as tight-knit as their anatomical proximity. Katz et al. (2000) suggest that gustation should be thought of as an integral part of a distributed, interacting multimodal system. In contrast to most other sensory systems, gustatory function is distributed among three different cranial nerves, which makes taste difficult to eliminate and, secondly, also difficult to distinguish from trigeminal perception (Prichard, 2011). The observation that taste buds degenerate after dissection of their sensory innervation and, subsequently, reappear after regeneration of their peripheral nerves has been a major focus of research in the peripheral taste system. Nineteenth- and early twentieth-century literature on taste bud degeneration, regeneration, and development was reviewed comprehensively by Parker (1922). Olmsted (1920) proposed that trophic maintenance of fish taste buds depended on the transmission of a putative trophic material from nerve to epithelium. Cross reinnervation of the glossopharyngeal nerve to fungiform taste buds (which are normally supplied by the chorda tympani) had no effect on the usual immunohistochemical properties of fungiform versus vallate taste buds (Smith et al., 1999). As a consequence, these authors believe that the protein expression in and subsequent function of taste buds depend on the epithelium from which the cells arise, and not the buds’ specific nerve supply. Meanwhile, Nosrat and Olson (1995) and Nosrat et al. (2000) detected mRNA of brain-derived neurotrophic factor (BDNF) and neurotrophins in developing anterior tongue epithelium, before nerve fibers were
655
observed. In BDNF-overexpressing mice, larger taste buds and more taste cells have been observed (Nosrat et al., 2012). This argues for the hypothesis that trophic factors act as target-derived chemoattractants for the early nerve fibers. These, in turn, initiate the formation of taste buds. BDNF-null mutant mice fail to develop taste buds (Oakley et al., 1998). Sensory ganglia involved in taste bud innervation (see above) are reduced by 40% in volume compared to about 20% of trigeminal ganglion under the same condition (Mistretta et al., 1999). Taste buds do not develop after injection of ß-bungarotoxin into the amniotic fluid in fetal mice. This neurotoxin abolishes motor and sensory nerve development (Morris-Wiman et al., 1999). Although nerve fibers are required to maintain taste buds once the latter are formed and start to function (e.g., Hosley et al., 1987; Yee et al., 2005), nerves seem not to be necessary to initiate taste bud development. Initial taste bud development is nerve-independent, suggested by a series of studies in salamanders (Stone, 1940), axolotl (Barlow et al., 1996; Barlow and Northcutt, 1998a,b) and mouse (Mbiene and Roberts, 2003). Taste buds seem to develop from local epithelium and not from neurogenic ectoderm [axolotl: Barlow and Northcutt (1997), mouse: Stone et al. (1995)]. It may be that mechanisms of differentiation of the same receptor organ vary among vertebrate taxa (Barlow, 2003). Growth factors other than BDNF may contribute to the maintenance of gustatory papillae, for example, epidermal growth factor (EGF) supplied by salivary glands (Liu et al., 2008; Morris-Wiman et al., 2000). More detailed studies on developmental aspects of the peripheral gustatory system including whether taste buds may develop without the stimulation of nerves are described later in this book (Chapter 33).
ACKNOWLEDGEMENTS The authors are indebted to Dr. Inglis Miller, Jr. who wrote a previous version of this chapter in the first edition, and Mihnea Nicolescu, who provided the schematic drawings. Drs. Judith and Donald Ganchrow helped with critical reading of an earlier version of the manuscript.
REFERENCES Albinus (1754). Academicarum annotationum libri I-VIII. liber I, Tab.I, Lugdunum Bataviensis (Leiden). Alcock, B. (1836). Determination of the question, which are the nerves of taste. Dublin. J. Med. Chem. Sci. 10: 256–279. Arey, L., Tremaine, M., and Monzingo, F. (1935). The numerical and topographical relation of taste buds to human circumvallate papillae throughout the life span. Anat. Rec. 64: 9–25. Arnold, F. (1839). Tabulae Anatomicae. Icones organum sensuum. Organon gustus. Fasc. secundus. Orellii, Fuesslini, Zürich.
656
Chapter 29
Anatomy of the Tongue and Taste Buds
Arvidson, K., and Friberg, U. (1980). Human taste: response and taste bud number in fungiform papillae. Science 209: 807–808. Astbäck, J., Arvidson, K., and Johansson, O. (1997). An immunohistochemical screening of neurochemical markers in fungiform papillae and taste buds of the anterior rat tongue. Arch. Oral. Biol. 42(2): 137–147. Atema, J. (1971). Structures and functions of the sense of taste in the catfish (Ictalurus natalis). Brain. Behav. Evol. 4(4): 273–294. Azen, E. A., Hellekant, G., Sabatini, L. M., and Warner, T. F. (1990). mRNAs for PRPs, statherin, and histatins in von Ebner’s gland tissues. J. Dent. Res. 69: 1724–1730. Azzali, G., Gennari, P. U., Maffei, G., and Ferri, T. (1996). Vallate, foliate and fungiform human papillae gustatory cells. An immunocytochemical and ultrastructural study. Minerva Stomatol. 45(9): 363–379. Azzali, G. (1997). Ultrastructure and immunocytochemistry of gustatory cells in man. Anat. Anz. 179(1): 37–44. Barlow, L. A. (2003). Toward a unified model of vertebrate taste bud development. J. Comp. Neurol. 457(2): 107–110. Barlow, L. A., Chien, C. B., and Northcutt, R. G. (1996). Embryonic taste buds develop in the absence of innervation. Development 122: 1103–1111. Barlow, L. A., and Northcutt, R. G. (1997). Taste buds develop autonomously from endoderm without induction by cephalic neural crest or paraxial mesoderm. Development 124(5): 949–957. Barlow, L. A., and Northcutt, R. G. (1998a). The role of innervation in the development of taste buds: insights from studies of amphibian embryos. Ann. N. Y. Acad. Sci. 855: 58–69. Barlow, L. A., and Northcutt, R. G. (1998b). Vertebrate taste-bud development: are salamanders the model? Reply. Trends Neurosci. 21(8): 338–338. Barreiro-Iglesias, A., Anadon, R., and Rodicio, M. C. (2010). The gustatory system of lampreys. Brain Behav. Evol. 75(4): 241–250. Bartel, D. L., Sullivan, S. L., Lavoie, E. G., et al.(2006). Nucleoside triphosphate diphosphohydrolase-2 is the ecto-ATPase of type I cells in taste buds. J. Comp. Neurol. 497(1): 1–12. Behrens, M., Born, S., Redel, U., et al. (2012). Immunohistochemical Detection of TAS2R38 Protein in Human Taste Cells. PLoS One 7(7): e40304. Beidler, L. M., and Smallman, R. L. (1965). Renewal of cells within taste buds. J. Cell Biol. 27: 263–272. Bellini, L. (1665). Gustus organum novissime deprehensum praemissis ad faciliorem intelligentiam quibusdam de saporibus (Taste organs newly observed; with certain premises about the senses given for easier understanding (translation from Latin into German by Jurisch (1922)). Mangetus Bibliotheca anat.2, Bologna. Berkhoudt, H. (1985). Special sense organs: Structure and function of avian taste receptors. In Form and function in birds, King, A. S. and McIelland, J. (Eds). Vol. 3, Academic Press, New York, pp. 463–496. Berridge, K. C., and Fentress, J. C. (1985). Trigeminal-taste interaction in palatability processing. Science 228(4700): 747–750. Borg, G., Diamant, H., Oakley, B., et al. (1967). A comparative study of neural and psychophysical responses to gustatory stimuli. In Olfaction and Taste 2, Hayashi, T. (Ed). Pergamon Press, Oxford, pp. 253–265. Boudriot, F., and Reutter, K. (2001). Ultrastructure of the taste buds in the blind cave fish Astyanax jordani (“Anoptichthys”) and the sighted river fish Astyanax mexicanus (Teleostei, Characidae). J. Comp. Neurol. 434(4): 428–444. Boughter Jr.,, J. D., Pumplin, D. W., Yu, C., et al. (1997). Differential Expression of alpha—Gustducin in Taste Bud Populations of the Rat and Hamster. J. Neurosci. 17(8): 2852–2858.
Bourgery, J. M., and Jacob, N. H. (1839). Organes de la digestion, de la dépuration urinaire et de la génération. Embryotomie. In Traité complet de l’anatomie de l’homme, Delaunay, C. A. (Ed). Vol. 5, Jules Didot L’Ainé, Paris, pp. Bradley, R. M. (1972). Development of the taste bud and gustatory papillae in human fetuses. In Third symposium on oral sensation and perception, Bosma, J. F. (Ed). Charles C Thomas, Springfield, Ill., USA, pp. 137–162. Bradley, R. M. (1973). Electrophysiological investigations of intravascular taste using perfused rat tongue. Am. J. Physiol. 224(2): 300–304. Bradley, R. M. (2000). Sensory receptors of the larynx. Am. J. Med. 108 Suppl 4a: 47S–50S. Bradley, R. M., Stedman, H. M., and Mistretta, C. M. (1983). Superior laryngeal nerve response patterns to chemical stimulation of sheep epiglottis. Brain Res. 276(1): 81–93. Bradley, R. M., and Stern, I. B. (1967). The development of the human taste bud during the foetal period. J. Anat. 101: 743–752. Braus, H. (1940). Handbuch der Mikroskopischen Anatomie des Menschen. Springer, Berlin. Bull, T. R. (1965). Taste and the chorda tympani. J. Laryngol. Otol. 79: 479–493. Burkl, W. (1954). Über das Vorkommen von Geschmacksknospen im mittleren Drittel des Oesophagus. Anat. Anz. 100: 320–321. Caicedo, A., Kim, K. N., and Roper, S. D. (2000). Glutamate-induced cobalt uptake reveals non-NMDA receptors in rat taste cells. J. Comp. Neurol. 417(3): 315–324. Cao, Y., Zhao, F. L., Kolli, T., et al. (2009). GABA expression in the mammalian taste bud functions as a route of inhibitory cell-to-cell communication. Proc. Natl. Acad. Sci. U.S.A. 106(10): 4006–4011. Carus, C. G. (1849). System der Physiologie. 2nd ed. Brockhaus, Leipzig. Casserius (1609). Penthaesteseion (cited after Jurisch, 1922). Chaudhari, N., and Roper, S. D. (2010). The cell biology of taste. J. Cell Biol. 190(3): 285–296. Cheng, L. H., and Robinson, P. P. (1991). The distribution of fungiform papillae and taste buds on the human tongue. Arch. Oral Biol. 36: 583–589. Cheng, S. J., Huang, C. F., Chen, Y. C., et al. (2009). Ultrastructural changes of posterior lingual glands after hypoglossal denervation in hamsters. J. Anat. 214(1): 163–170. Clapp, T. R., Stone, L. M., Margolskee, R. F., and Kinnamon, S. C. (2001). Immunocytochemical evidence for co-expression of Type III IP3 receptor with signaling components of bitter taste transduction. BMC Neurosci. 2: 6. Clapp, T. R., Yang, R., Stoick, C. L., et al. (2004). Morphologic characterization of rat taste receptor cells that express components of the phospholipase C signaling pathway. J. Comp. Neurol. 468(3): 311–321. Connes, R., Granie-Prie, M., Diaz, J. P., and Paris, J. (1988). Ultrastructure des bourgeons du gout du téléostéen marin Dicentrarchus labrax L. Can. J. Zool. 66: 2133–2142. Cottler Fox, M., Arvidson, K., Hammarlund, E., and Friberg, U. (1987). Fixation and occurrence of dark and light cells in taste buds of fungiform papillae. Scand. J. Dent. Res. 95: 417–427. Cruz, A., and Green, B. G. (2000). Thermal stimulation of taste. Nature 403(6772): 889–892. Cummings, T. A., Delay, R. J., and Roper, S. D. (1987). Ultrastructure of apical specializations of taste cells in the mudpuppy, Necturus maculosus. J. Comp. Neurol. 261(4): 604–615. Dando, R., and Roper, S. D. (2009). Cell-to-cell communication in intact taste buds through ATP signalling from pannexin 1 gap junction hemichannels. J. Physiol. 587(Pt 24): 5899–5906.
References Davis, C. (1877). Die becherförmigen Organe des Kehlkopfs. Arch. mikr. Anat. 14: 158–167. DeFazio, R. A., Dvoryanchikov, G., Maruyama, Y., et al. (2006). Separate populations of receptor cells and presynaptic cells in mouse taste buds. J. Neurosci. 26(15): 3971–3980. Delay, R. J., Kinnamon, S. C., and Roper, S. D. (1997). Serotonin modulates voltage-dependent calcium current in Necturus taste cells. J. Neurophysiol. 77(5): 2515–2524. Delay, R. J., Mackay Sim, A., and Roper, S. D. (1994). Membrane properties of two types of basal cells in Necturus taste buds. J. Neurosci. 14: 6132–6143. Delay, R. J., and Roper, S. D. (1988). Ultrastructure of taste cells and synapses in the mudpuppy Necturus maculosus. J. Comp. Neurol. 277: 268–280. Delay, R. J., Taylor, R., and Roper, S. D. (1993). Merkel-like basal cells in Necturus taste buds contain serotonin. J. Comp. Neurol. 335(4): 606–613. Desgranges, J. C. (1965). Sur l’existence de plusieurs types de cellules sensorielles dans les bourgeons du gout des barbillons du Poisson-chat. C.R. Acad. Sc.(Paris) 261: 1095–1098. Doty, R. L., Cummins, D. M., Shibanova, A., et al. (2009). Lingual distribution of the human glossopharyngeal nerve. Acta Otolaryngol. 129(1): 52–56. Dvoryanchikov, G., Sinclair, M. S., Perea-Martinez, I., et al. (2009). Inward rectifier channel, ROMK, is localized to the apical tips of glial-like cells in mouse taste buds. J. Comp. Neurol. 517(1): 1–14. Ebner, V. (1873). Die acinösen Drüsen der Zunge und ihre Beziehungen zu den Geschmacksorganen. Leuschner & Lubensky, Graz. Ehrenberg, C. G. (1833). Notwendigkeit einer feineren mechanischen Zerlegung des Gehirns und der Nerven vor der chemischen, dargestellt an Beobachtungen von C.G.Ehrenberg. Poggendorfs Annl. Physik. Chemie. XXVIII: 450. Ehrlich, P. (1886). Über die Methylenblaureaktion der lebenden Nervensubstanz. Deutsche Med. Wochenschr. 12: 49–52. Engelmann, T. W. (1872). Die Geschmacksorgane. In Handbuch der Lehre von den Geweben des Menschen und der Thiere, Stricker, S. (Ed). Vol. 2, Engelmann, Leipzig, pp. 822–838. Engström, H., and Rytzner, C. (1956). The fine structure of taste buds and taste fibers. 361–375 65. Fährmann, W. (1967). [Light and electron microscopical studies on the taste bud of neotene axolotls (Siredon mexicanum Shaw)]. Z. Mikrosk. Anat. Forsch. 77: 117–152. Farbman, A. I. (1965). Electron microscope study of the developing taste bud in rat fungiform papilla. Dev. Biol. 11: 110–135. Farbman, A. I. (1980). Renewal of taste bud cells in rat circumvallate papillae. Cell Tissue Kinet. 13: 349–357. Farbman, A. I., and Hellekant, G. (1978). Quantitative analyses of the fiber population in rat chorda tympani nerves and fungiform papillae. Am. J. Anat. 153: 509–521. Farbman, A. I., Hellekant, G., and Nelson, A. (1985). Structure of taste buds in foliate papillae of the rhesus monkey, Macaca mulatta. Am. J. Anat. 172(1): 41–56. Farbman, A. I., Ogden Ogle, C. K., Hellekant, G., et al. (1987). Labeling of sweet taste binding sites using a colloidal gold- labeled sweet protein, thaumatin. Scanning. Microsc. 1: 351–357. Farbman, A. I., and Yonkers, J. D. (1971). Fine structure of the taste bud in the mud puppy, Necturus maculosus. Am. J. Anat. 131: 353–369. Feneis, H. (1985). Pocket Atlas of human anatomy. Thieme, New York. Ferrando, S., Gallus, L., Gambardella, C., et al. (2012). First detection of taste buds in a chimaeroid fish (Chondrichthyes: Holocephali) and their Galphai-like immunoreactivity. Neurosci. Lett. 517(2): 98–101.
657
Finger, T. E. (1997). Evolution of taste and solitary chemoreceptor cell systems. Brain Behav. Evol. 50(4): 234–243. Finger, T. E., Bottger, B., Hansen, A., et al. (2003). Solitary chemoreceptor cells in the nasal cavity serve as sentinels of respiration. Proc. Natl. Acad. Sci. U.S.A. 100(15): 8981–8986. Finger, T. E., Bryant, B. P., Kalinoski, D. L., et al. (1996). Differential localization of putative amino acid receptors in taste buds of the channel catfish, Ictalurus punctatus. J. Comp. Neurol. 373(1): 129–138. Finger, T. E., Danilova, V., Barrows, J., et al. (2005). ATP signaling is crucial for communication from taste buds to gustatory nerves. Science 310(5753): 1495–1499. Fixsen, C. (1857). De linguae raninae textura disquisitiones microscopicae. Diss. inaug. Dorpati Livonor. Froriep, R. (1828). De lingua anatomica quaedam et semiotica. Fujimoto, S., Ueda, H., and Kagawa, H. (1987). Immunocytochemistry on the localization of 5-hydroxytryptamine in monkey and rabbit taste buds. Acta Anat. 128: 80–83. Fukami, H., and Bradley, R. M. (2005). Biophysical and morphological properties of parasympathetic neurons controlling the parotid and von Ebner salivary glands in rats. J. Neurophysiol. 93(2): 678–686. Ganchrow, D., Ganchrow, J. R., and Goldstein, R. S. (1991). Ultrastructure of palatal taste buds in the perihatching chick. Am. J. Anat. 192(1): 69–78. Ganchrow, J. R., and Ganchrow, D. (1987). Taste bud development in chickens (Gallus gallus domesticus). Anat. Rec. 218: 88–93. Ganchrow, J. R., Ganchrow, D., and Oppenheimer, M. (1986). Chorda tympani innervation of anterior mandibular taste buds in the chicken (Gallus gallus domesticus). Anat. Rec. 216(3): 434–439. Ganchrow, J. R., Ganchrow, D., Royer, S. M., and Kinnamon, J. C. (1993). Aspects of vertebrate gustatory phylogeny: morphology and turnover of chick taste bud cells. Microsc. Res. Tech. 26: 106–119. Gerlach, J. (1858). Mikroskopische Studien aus dem Gebiet der menschlichen Morphologie. F. Enke, Erlangen. Getchell, T. V., Margolis, F. L., and Getchell, M. L. (1984). Perireceptor and receptor events in vertebrate olfaction. Prog. Neurobiol. 23: 317–345. Golgi, C. (1873). Sulla struttura della sostanza grigia del cervello (comunicazione preventiva). Gazzetta Medica Italiana-Lombardia 33: 244 –246. Gråberg, J. (1898). Beiträge zur Genese des Geschmacksorgans des Menschen. Morphol. Arb. 8: 117–134. Graziadei, P. P., and DeHan, R. S. (1971). The ultrastructure of frogs’ taste organs. Acta Anat. (Basel) 80(4): 563–603. Grover Johnson, N., and Farbman, A. I. (1976). Fine structure of taste buds in the barbel of the catfish, Ictalurus punctatus. Cell Tissue Res. 169: 395–403. Gurkan, S., and Bradley, R. M. (1987). Autonomic control of von Ebner’s lingual salivary glands and implications for taste sensation. Brain Res. 419: 287–293. Habermehl, K. H. (1952). Über besondere Randpapillen an der Zunge neugeborener Säugetiere. Z. Anat. Entwickl. Gesch. 116: 355–372. Haller, A. v. (1766). Gustus. In Elementa physiologiae Vol. IV, V, F.Grasset, Lausanne, pp. 99–124. Hamasaki, K., Seta, Y., Yamada, K., and Toyoshima, K. (1998). Possible role of serotonin in Merkel-like basal cells of the taste buds of the frog, Rana nigromaculata. J. Anat. 193(4): 599–610. Hannover, A. (1840). Die Chromsäure, ein vorzügliches Mittel bei mikroskopischen Untersuchungen. Müllers Archiv: 549–558. Harada, S., and Smith, D. V. (1992). Gustatory sensitivities of the hamster’s soft palate. Chem. Senses 17: 37–51. Harris, W. (1952). The fifth and seventh nerves in relation to the nervous mechanism of taste sensation: a new approach. Brit. Med. J. 1: 831–836.
658
Chapter 29
Anatomy of the Tongue and Taste Buds
Hellekant, G. (1976). The blood circulation of the tongue. In Frontiers of Oral Physiology, Kawamura, Y. (Ed). S. Karger, Basel, pp. 130–145. Hellman, T. J. (1922). Die Genese der Zungenpapillen beim Menschen. Ups. Läkaref. Förh. 26,5–6: 1–69. Helmholtz (1842). De fabrica systematis nervosi evertebratorum. Dissertation, University of Berlin. Hermann, F. (1885). Beittrag zur Entwicklungsgeschichte des Geschmacksorgans beim Kaninchen. Arch. f. Mikroskop. Anat. Entwicklungsmech. 24: 216–229. Herness, M. S. (1989). Vasoactive intestinal peptide-like immunoreactivity in rodent taste cells. Neuroscience 33(2): 411–419. Herness, S., Zhao, F. L., Lu, S. G., et al. (2002). Expression and physiological actions of cholecystokinin in rat taste receptor cells. J. Neurosci. 22(22): 10018–10029. Herrick, C. J. (1904). The organ and sense of taste in fishes. U.S. Fish Comm. Bull. 1902 (abstracted in J. Comp. Neurol. Psych. 277–278, 1904): 237–272. Hersch, M., and Ganchrow, D. (1980). Scanning electron microscopy on human embryonic and fetal tongue. Chem. Senses 5: 331–341. Hinrichsen, K. V. (1990). Humanembryologie. Lehrbuch und Atlas der vorgeburtlichen Entwicklung des Menschen. (Hinrichesen, K. V., ed.) Berlin, Heidelberg, New York, Springer Verlag. Hirata, Y. (1966). Fine structure of the terminal buds on the barbels of some fishes. Arch. Histol. Jpn. 26(5): 507–523. Höfer, D., and Drenckhahn, D. (1999). Localisation of actin, villin, fimbrin, ezrin and ankyrin in rat taste receptor cells. Histochem. Cell Biol. 112(1): 79–86. Hofer, H., Meinel, W., and Rommel, C. (1979). Taste buds in the epithelium of the plica sublingualis of New World monkeys. Anat. Anz. 145(1): 17–31. Hoffmann, A. (1875). Ueber die Verbreitung der Geschmacksknospen beim Menschen. Arch. pathol. Anat. Physiol. klin. Med. 62: 516–530. Hokfelt, T., Lundberg, J. M., Schultzberg, M., et al. (1980). Cellular localization of peptides in neural structures. Proc. R. Soc. Lond B. Biol. Sci. 210(1178): 63–77. Hönigschmied, J. (1873). Beiträge zur mikroskopischen Anatomie über die Geschmacksorgane der Säugethiere. Zeitschr. Wiss. Zoologie 23: 414–434. Hoon, M. A., Adler, E., Lindemeier, J., et al. (1999). Putative mammalian taste receptors: a class of taste-specific GPCRs with distinct topographic selectivity. Cell 96(4): 541–551. Hoon, M. A., Northup, J. K., Margolskee, R. F., and Ryba, N. J. (1995). Functional expression of the taste specific G-protein, alpha-gustducin. Biochem. J. 309(Pt 2): 629–636. Hosley, M. A., Hughes, S. E., and Oakley, B. (1987). Neural induction of taste buds. J. Comp. Neurol. 260: 224–232. Hou-Jensen, H. (1933). Die Papillae foliatae des Menschen. Z. Anat. Entwicklgesch. 102: 348–388. Hu, Z. L., Masuko, S., and Katsuki, T. (1996). Distribution and origins of nitric oxide-producing nerve fibers in the dog tongue: correlated NADPH-diaphorase histochemistry and immunohistochemistry for calcitonin gene-related peptide using light and electron microscopy. Arch. Histol. Cytol. 59(5): 491–503. Huang, Y.-J., Maruyama, Y., Lu, K.-S., et al. (2005). Mouse Taste Buds Use Serotonin as a Neurotransmitter. J. Neurosci. 25(4): 843–847. Huang, Y. A., Dando, R., and Roper, S. D. (2009). Autocrine and paracrine roles for ATP and serotonin in mouse taste buds. J. Neurosci. 29(44): 13909–13918. Huang, Y. A., Maruyama, Y., Stimac, R., and Roper, S. D. (2008). Presynaptic (Type III) cells in mouse taste buds sense sour (acid) taste. J. Physiol. 586(12): 2903–2912.
Hunt, J. R. (1915). The sensory field of the facial nerve: a further contribution to the symptomatology of the geniculate ganglion. Brain 38: 418–446. Iida, M., Yoshioka, I., and Muto, H. (1983). Taste bud papillae on the retromolar mucosa of the rat, mouse and golden hamster. Acta Anat. Basel. 117: 374–381. Ito, A., and Nosrat, C. A. (2009). Gustatory papillae and taste bud development and maintenance in the absence of TrkB ligands BDNF and NT-4. Cell Tissue Res. 337(3): 349–359. Iwasaki, S., Yoshizawa, H., and Kawahara, I. (1996). Three-dimensional ultrastructure of the surface of the tongue of the rat snake, Elaphe climacophora. Anat. Rec. 245(1): 9–12. Jägel. (1991). Zur Geschichte der Anatomie und Physiologie des Geschmackssinnes. Diss. Univ. Kiel: 1–118. Jaeger, C.B., Hillmann, D.E. (1976). Gustatory system. Morphology of gustatory organs. In Frog neurobiology A Handbook, R. Llinás, and W. Precht, eds. (Berlin, Heidelberg, New York: Springer), pp. 588–606. Jain, S., and Roper, S. D. (1991). Immunocytochemistry of gamma-aminobutyric acid, glutamate, serotonin, and histamine in Necturus taste buds. J. Comp. Neurol. 307(4): 675–682. Jakubowski, and Whitear, M. (1986). Ultrastructure of taste buds in fishes. Folia Histochem. Cytobiol. 24: 310–311. Jowett, A., and Shrestha, R. (1998). Mucosa and taste buds of the human epiglottis. J. Anat. 193(4): 617–618. Jeffery, W. R., Strickler, A. G., Guiney, S., et al. (2000). Prox 1 in eye degeneration and sensory organ compensation during development and evolution of the cavefish Astyanax. Dev. Genes. Evol. 210(5): 223–230. Jurisch, A. (1922). Studien über die Papillae vallatae beim Menschen. Z. Anat. Entwicklungsgesch. 66: 1–149. Just, T., Pau, H. W., Bombor, I., et al. (2005). Confocal microscopy of the Peripheral Gustatory System: Comparison between Healthy Subjects and Patients Suffering from Taste Disorders during Radiochemotherapy. Laryngoscope 115(12): 2178–2182. Kaya, N., Shen, T., Lu, S.-g., et al. (2004). A paracrine signaling role for serotonin in rat taste buds: expression and localization of serotonin receptor subtypes. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 286(4): R649–R658. Katz, D. B., Nicolelis, M. A., and Simon, S. A. (2000). IV. There is more to taste than meets the tongue. Am. J. Physiol. Gastrointest Liver Physiol. 278(1): G6–G9. Kim, D. J., and Roper, S. D. (1995). Localization of serotonin in taste buds: a comparative study in four vertebrates. J. Comp. Neurol. 353: 364–370. Kim, M. R., Kusakabe, Y., Miura, H., et al. (2003). Regional expression patterns of taste receptors and gustducin in the mouse tongue. Biochem. Biophys. Res. Commun. 312(2): 500–506. Kinnamon, J. C., Henzler, D. M., and Royer, S. M. (1993). HVEM ultrastructural analysis of mouse fungiform taste buds, cell types, and associated synapses. Microsc. Res. Tech. 26: 142–156. Kinnamon, J. C., McPheeters, M. M., and Kinnamon, S. C. (1994). Structure/Function correlates in taste buds. In: Olfaction and Taste (K.Kurihara, N Suzuki, H Ogawa, eds), Springer-Verlag, Tokyo, Berlin, Heidelberg, New York, London, Paris XI: 9–12. Kinnamon, J. C., Sherman, T. A., and Roper, S. D. (1988). Ultrastructure of mouse vallate taste buds: III. Patterns of synaptic connectivity. J. Comp. Neurol. 270: 1–10, 56. Kinnamon, J. C., Taylor, B. J., Delay, R. J., and Roper, S. D. (1985). Ultrastructure of mouse vallate taste buds. I. Taste cells and their associated synapses. J. Comp. Neurol. 235: 48–60. Kinnamon, S. C. (2011). Taste receptor signalling—from tongues to lungs. Acta Physiol. (Oxf) 204(2): 158–168.
References Kishi, M., Emori, Y., Tsukamoto, Y., and Abe, K. (2001). Primary culture of rat taste bud cells that retain molecular markers for taste buds and permit functional expression of foreign genes. Neuroscience 106(1): 217–225. Kishi, M., Emori, Y., Tsukamoto, Y., and Abe, K. (2002). Changes in cell morphology and cell-to-cell adhesion induced by extracellular Ca2+ in cultured taste bud cells. Biosci. Biotechnol. Biochem. 66(2): 484–487. Koelliker, R. A. (1844). Die Selbständigkeit und Abhängigkeit des sympathischen Nervensystems durch anatomische Beobachtungen bewiesen. Ein akademisches Programm. U.Zeller, Zürich. Korte, G. E. (1979). Unusual association of ‘chloride cells’ with another cell type in the skin of the glass catfish, Kryptopterus bicirrhis. Tissue Cell 11(1): 63–68. Kotrschal, K. (1996). Solitary chemosensory cells: Why do primary aquatic vertebrates need another taste system. Trends Ecol.Evol. 11: 110–114. Krause, R. (1911). Kursus der normalen Histologie. (American edition: Rebman Co., N.Y.) ed. Urban und Schwarzenberg, Berlin and Wien. Kudo, K., Wakamatsu, K., Nishimura, S., and Tabata, S. (2010). Gustducin is expressed in the taste buds of the chicken. Anim. Sci. J. 81(6): 666–672. Lalonde, E., and Eglitis, J. (1961). Number and distribution of taste buds on the epiglottis, pharynx, larynx, soft palate and uvula in a human newborn. Anat.Rec. 140: 91–95. Landin, A. M., Kim, J. W., and Chaudhari, N. (2005). Liposome-mediated transfection of mature taste cells. J. Neurobiol. 65(1): 12–21. Lawton, D. M., Furness, D. N., Lindemann, B., and Hackney, C. M. (2000). Localization of the glutamate-aspartate transporter, GLAST, in rat taste buds. Eur. J. Neurosci. 12(9): 3163–3171. Lewis, D., and Dandy, W. E. (1930). The course of the nerve fibers transmitting sensation of taste. Arch.Surg. 21: 249–288. Leydig, F. (1851). Über die Haut einiger Süßwasserfische. Z. Wiss. Zool. 3: 1–12. Li, J. H., and Lindemann, B. (2003). Multi-photon microscopy of cell types in the viable taste disk of the frog. Cell Tissue Res. 313(1): 11–27. Li, X. J., and Snyder, S. H. (1995). Molecular cloning of Ebnerin, a von Ebner’s gland protein associated with taste buds. J. Biol. Chem. 270(30): 17674–17679. Lin, W., and Kinnamon, S. C. (1999). Co-localization of epithelial sodium channels and glutamate receptors in single taste cells. Biol. Signals Recept. 8(6): 360–365. Lindemann, B. (1996). Taste reception. Physiol. Rev. 76: 719–766. Linden, R. W. (1993). Taste. Br. Dent J. 175(7): 243–253. Liu, H. X., Henson, B. S., Zhou, Y., et al. (2008). Fungiform papilla pattern: EGF regulates inter-papilla lingual epithelium and decreases papilla number by means of PI3K/Akt, MEK/ERK, and p38 MAPK signaling. Dev. Dyn. 237(9): 2378–2393. Liu, L., and Simon, S. A. (1998). Responses of cultured rat trigeminal ganglion neurons to bitter tastants. Chem. Senses 23(2): 125–130. Lovén, C. (1868). Beiträge zur Kenntnis vom Bau der Geschmackswärzchen der Zunge. Arch. Mikrosk. Anat. IV: 96–110. Lussana, F. (1869). Recherches expérimentales et observations pathologiques sur les nerfs du gout. Arch. phys. (Paris) 2: 197–210. Lussana, F. (1872). Sur les nerfs du gout. Observations et expériences nouvelles. Arch. phys. (Paris) 4: 334–350. Ma, H., Yang, R., Thomas, S. M., and Kinnamon, J. C. (2007). Qualitative and quantitative differences between taste buds of the rat and mouse. BMC Neurosci. 8: 5. Magendie, F. (1820). Grundriss der Physiologie (translated from French by C.F. Heusinger). Baercke, Eisenach. Malpighi, M. (1686). Exercitatio epistolica de lingua. ( 1664; Jo. Alphonso Borellio). In Opera omnia, Malpighi, M. (Ed). R.Scott & G. Wells, Londini, pp. 13–20.
659
Matsunami, H., Montmayeur, J. P., and Buck, L. B. (2000). A family of candidate taste receptors in human and mouse. Nature 404(6778): 601–604. Mbiene, J. P., and Roberts, J. D. (2003). Distribution of keratin 8-containing cell clusters in mouse embryonic tongue: evidence for a prepattern for taste bud development. J. Comp. Neurol. 457(2): 111–122. McLaughlin, S. K., McKinnon, P. J., and Margolskee, R. F. (1992). Gustducin is a taste-cell-specific G protein closely related to the transducins. Nature 357(6379): 563–569. Menco, B. P. (1989). Olfactory and nasal respiratory epithelia, and foliate taste buds visualized with rapid-freeze freeze-substitution and Lowicryl K11M embedding. Ultrastructural and initial cytochemical studies. Scanning. Microsc. 3: 257–272. Menco, B. P. M., Yankova, M. P., and Simon, S. A. (1997). Freeze- substitution and postembedding immunocytochemistry on rat taste buds: G-proteins, calcitonin gene-related peptide, and choline acetyl transferase. Microsc. Microanal. 3: 53–69. Merkel, F. (1880). Ueber die Endigungen der sensiblen Nerven in der Haut der Wirbelthiere. Stiller, Rostock. Miller, I. J., Jr., and Bartoshuk, L. M. (1991). Taste perception, taste bud distribution, and spatial relationships. 1 ed. In Smell and taste in health and disease, Getchell, T. V., Bartoshuk, L. M., Doty, R. L. and Snow, J. B. J., Jr., (Eds). New York, Raven Press, pp. 205–233. Miller, I. J., Jr., and Reedy, F. E., Jr., (1990a). Variations in human taste bud density and taste intensity perception. Physiol. Behav. 47(6): 1213–1219. Miller, I. J., Jr., and Reedy, F. E. J. (1990b). Quantification of fungiform papillae and taste pores in living human subjects. Chem. Senses 15: 281–294. Miller, I. J., Jr., and Smith, D. V. (1984). Quantitative taste bud distribution in the hamster. Physiol.Behav. 32: 275–285. Miller, I. J., Jr., and Spangler, K. M. (1982). Taste bud distribution and innervation on the palate of the rat. Chem. Senses 7: 99–108. Mistretta, C. M., and Baum, B. J. (1984). Quantitative study of taste buds in fungiform and circumvallate papillae of young and aged rats. J. Anat. 138: 323–332. Mistretta, C. M., Goosens, K. A., Farinas, I., and Reichardt, L. F. (1999). Alterations in size, number, and morphology of gustatory papillae and taste buds in BDNF null mutant mice demonstrate neural dependence of developing taste organs. J. Comp. Neurol. 409(1): 13–24. Miura, H., Scott, J. K., Harada, S., Barlow, L. A. (2014). Sonic hedgehog-expressing basal cells are general post-mitotic precursors of functional taste receptor cells. Dev. Dyn. 243: 1286–1297. Mochizuki, Y. (1939). Studies of the papilla foliata of Japanese. Okajimas Folia Anat. Jpn. 18: 334–369. Moll, R. (1993). Cytokeratins as markers of differentiation: Expression profiles in epithelia and epithelial tumors. In Progress in Pathology, Seifert, G. (Ed). Vol. 142, G. Fischer, Stuttgart, Jena, New York, pp. 1–197. Montavon, P., Hellekant, G., and Farbman, A. (1996). Immunohistochemical, electrophysiological, and electron microscopical study of rat fungiform taste buds after regeneration of chorda tympani through the non-gustatory lingual nerve. J. Comp. Neurol. 367: 491–502. Morris-Wiman, J., Basco, E., and Du, Y. (1999). The effects of beta-bungarotoxin on the morphogenesis of taste papillae and taste buds in the mouse. Chem. Senses 24(1): 7–17. Morris-Wiman, J., Sego, R., Brinkley, L., and Dolce, C. (2000). The effects of sialoadenectomy and exogenous EGF on taste bud morphology and maintenance [In Process Citation]. Chem. Senses 25(1): 9–19. Münch, F. (1896). Die Topographie der Papillen Zunge des Menschen und der Säugethiere. Morphol. Arb. Schwalbe 6: 605. Murray, R. G. (1973). The ultrastructure of taste buds. In The Ultrastructure of Sensory Organs, Friedmann, I. (Ed). North Holland publishing company, Amsterdam, London, pp. 1–81.
660
Chapter 29
Anatomy of the Tongue and Taste Buds
Murray, R. G. (1986). The mammalian taste bud type III cell: a critical analysis. J. Ultrastruct. Mol. Struct. Res. 95: 175–188. Murray, R. G., and Murray, A. (1967). Fine structure of taste buds of rabbit foliate papillae. J. Ultrastruct. Res. 19: 327–353. Murray, R. G., and Murray, A. (1971). Relations and possible significance of taste bud cells. Contrib. Sens. Physiol. 5: 47–95. Murray, R. G., Murray, A., and Fujimoto, S. (1969). Fine structure of gustatory cells in rabbit taste buds. J.Ultrastruct.Res. 27: 444–461. Nada, O., and Hirata, K. (1977). The monoamine-containing cell in the gustatory epithelium of some vertebrates. Arch. Histol. Jpn. 40 Suppl: 197–206. Nada, O., and Hirata, K. (1975). The occurrence of the cell type containing a specific monoamine in the taste bud of the rabbit’s foliate papila. Histochemistry 43(3): 237–240. Nagai, T., Kim, D. J., Delay, R. J., and Roper, S. D. (1996). Neuromodulation of transduction and signal processing in the end organs of taste. Chem. Senses 21(3): 353–365. Nagato, T., Ren, X. Z., Toh, H., and Tandler, B. (1997). Ultrastructure of Weber’s salivary glands of the root of the tongue in the rat. Anat. Rec. 249(4): 435–440. Nelson, G. M., and Finger, T. E. (1993). Immunolocalization of different forms of neural cell adhesion molecule (NCAM) in rat taste buds. J. Comp. Neurol. 336:507–516. Nemetschek-Ganssler, H., and Ferner, H. (1964). Über die Ultrastruktur der Geschmacksknospen. Z. Zellforsch. 63: 155–178. Nishijima, K., and Atoji, Y. (2004). Taste buds and nerve fibers in the rat larynx: an ultrastructural and immunohistochemical study. Arch. Histol. Cytol. 67(3): 195–209. Nolte, C., and Martini, R. (1992). Immunocytochemical localization of the L1 and N-CAM cell adhesion molecules and their shared carbohydrate epitope L2/HNK-1 in the developing and differentiated gustatory papillae of the mouse tongue. J.Neurocytol. 21: 19–33. Nomura, S., Shiba, Y., Muneoka, Y., and Kanno, Y. (1979). A scanning and transmission electron microscope study of the premetamorphic papillae: possible chemoreceptive organs in the oral cavity of an anuran tadpole (Rana japonica). Arch. Histol. Jpn. 42(5): 507–516. Norgren, R. (1990). Gustatory system. In The Human Nervous System, Paxinos, G. (Ed). Academic Press, San Diego, pp. 845–861. Nosrat, C. A., and Olson, L. (1995). Brain-derived neurotrophic factor mRNA is expressed in the developing taste bud-bearing tongue papillae of rat. J. Comp. Neurol. 360(4): 698–704. Nosrat, I. V., Lindskog, S., Seiger, A., and Nosrat, C. A. (2000). Lingual BDNF and NT-3 mRNA expression patterns and their relation to innervation in the human tongue: similarities and differences compared with rodents. J. Comp. Neurol. 417(2): 133–152. Nosrat, I. V., Margolskee, R. F., and Nosrat, C. A. (2012). Targeted taste cell-specific overexpression of brain-derived neurotrophic factor in adult taste buds elevates phosphorylated TrkB protein levels in taste cells, increases taste bud size, and promotes gustatory innervation. J. Biol. Chem. 287(20): 16791–16800.
Ogura, T., Margolskee, R. F., Tallini, Y. N., et al. (2007). Immuno- localization of vesicular acetylcholine transporter in mouse taste cells and adjacent nerve fibers: indication of acetylcholine release. Cell Tissue Res. 330(1): 17–28. Ohmura, S., Horimoto, S., and Fujita, K. (1989). Lectin cytochemistry of the dark granules in the type 1 cells of Syrian hamster circumvallate taste buds. Arch. Oral Biol. 34: 161–166. Ohshima, H., Yoshida, S., and Kobayashi, S. (1990). Blood vascular architecture of the rat lingual papillae with special reference to their relations to the connective tissue papillae and surface structures: a light and scanning electron microscope study. Acta. Anat. (Basel) 137(3): 213–221. Oike, H., Matsumoto, I., and Abe, K. (2006). Group IIA phospholipase A(2) is coexpressed with SNAP-25 in mature taste receptor cells of rat circumvallate papillae. J. Comp. Neurol. 494(6): 876–886. Ojima, K., Matsumoto, S., Takeda, M., et al. (1997a). Numerical variation and distributive pattern on microvascular cast specimens of vallate papillae in the crossbred Japanese cat tongue. Ann. Anat. 179(2): 117–126. Ojima, K., Takahashi, T., Matsumoto, S., et al. (1997b). Angioarchitectural structure of the fungiform papillae on rabbit tongue anterodorsal surface. Ann. Anat. 179(4): 329–333. Ojima, K., Takeda, M., Matsumoto, S., et al. (1997c). Functional role of V form distribution seen in microvascular cast specimens of the filiform and fungiform papillae on the posterior central dorsal surface of the cat tongue. Ann. Anat. 179(4): 321–327. Oka, Y., and Korsching, S. I. (2011). Shared and unique G alpha proteins in the zebrafish versus mammalian senses of taste and smell. Chem. Senses 36(4): 357–365. Olmsted, J. M. D. (1920). The results of cutting the seventh cranial nerve in Amiurus nebulosus (Leseur). J.Exp.Zool. 31: 369–401. Osculati, F., and Sbarbati, A. (1995). The frog taste disc: a prototype of the vertebrate gustatory organ. Prog Neurobiol 46, 351–399. Ozdener, H., Yee, K. K., Cao, J., et al. (2006). Characterization and Long-Term Maintenance of Rat Taste Cells in Culture. Chem. Senses 31(3): 279–290. Panizza, B. (1834). Ricerche sperimentali sopra i nervi. Bizzoni, Pavia. Paran, N., Mattern, C. F., and Henkin, R. I. (1975). Ultrastructure of the taste bud of the human fungiform papilla. Cell Tissue Res. 161: 1–10. Parker, G. H. (1922). Smell,Taste, and Allied Senses in the Vertebrates. Lippincott, London. Perez, C. A., Huang, L., Rong, M., et al. (2002). A transient receptor potential channel expressed in taste receptor cells. Nat. Neurosci. 5(11): 1169–1176. Pevzner, R. A., and Tikhonova, N. A. (1980). [Cytochemical demonstration of cyclic nucleotide phosphodiesterases in the taste buds of Testudo horsefieldi turtles upon exposure to flavored substances]. Zh. Evol. Biokhim Fiziol. 16(2): 133–136. Ponzo, M. (1907). Sulla presenza di organi del gusto nella parte laringea della faringe, nel tratto cervicale dellésofago e nel palato duro del feto umano. Anat.Anz. 31: 570–575.
Oakley, B. (1970). Reformation of taste buds by crossed sensory nerves in the rat’s tongue. Acta. Physiol. Scand 79(1): 88–94.
Prichard, T. C. (2011). Gustatory system. 3rd ed. In The Human Nervous System, Mai, J. K. and Paxinos, G. (Eds). Elsevier, Amsterdam, Boston, Heidelberg, pp. 1187–1218.
Oakley, B., Brandemihl, A., Cooper, D., et al. (1998). The morphogenesis of mouse vallate gustatory epithelium and taste buds requires BDNF-dependent taste neurons. Dev. Brain Res. 105(1): 85–96.
Pritchard, T. C. (1991). The Primate Gustatory System. In Smell and Taste in Health and Disease, Getchell, T. V., Bartoshuk, L. M., Doty, R. L. and Snow, J. B. J., Jr., (Eds). Raven Press, New York, pp. 109–125.
Obata, H., Shimada, K., Sakai, N., and Saito, N. (1997). GABAergic neurotransmission in rat taste buds: immunocytochemical study for GABA and GABA transporter subtypes. Brain Res. Mol. Brain Res. 49(1–2): 29–36.
Pumplin, D. W., and Getschman, E. (2000). Synaptic proteins in rat taste bud cells: appearance in the Golgi apparatus and relationship to alpha-gustducin and the Lewis(b) and A antigens. J. Comp. Neurol. 427(2): 171–184.
References Pumplin, D. W., Getschman, E., Boughter, J. D., Jr., et al. (1999). Differential expression of carbohydrate blood-group antigens on rat taste-bud cells: relation to the functional marker alpha-gustducin. J. Comp. Neurol. 415(2): 230–239. Pumplin, D. W., Yu, C., and Smith, D. V. (1997). Light and dark cells of rat vallate taste buds are morphologically distinct cell types. J. Comp. Neurol. 378(3): 389–410. Rabl, H. (1895). Notiz zur Morphologie der Geschmacksknospen auf der Epiglottis. Anat.Anz. 11: 153–156. Ranvier, L. (1888). Technisches Lehrbuch der Histologie (German translation by W.Nicati and H.v.Wyss). F.C.W.Vogel, Leipzig. Remak, R. (1852). Ueber die Ganglien der Zunge bei Säugethieren und beim Menschen. In Archiv für Anatomie, Physiologie und Wissenschaftliche Medicin, Müller, J. (Ed). Veit et Comp., Berlin, pp. 58–62. Ren, Y., Shimada, K., Shirai, Y., et al. (1999). Immunocytochemical localization of serotonin and serotonin transporter (SET) in taste buds of rat. Brain Res. Mol. Brain Res. 74(1–2): 221–224. Retzius, G. (1892). Die Nervenendigungen in dem Geschmacksorgan der Säugethiere und Amphibien. In Biologische Untersuchungen Neue Folge IV, Samson & Wallin, Stockholm, pp. 26–32. Retzius, G. (1893). Ueber Geschmacksknospen bei Petromyzon. In Biologische Untersuchungen. Neue Folge Vol. V, Samson & Wallin, Stockholm, pp. 69–70. Reutter, K. (1971). The taste-buds of Amiurus nebulosus (Lesueur). Morphological and histochemical investigations. Z. Zellforsch. Mikrosk. Anat. 120(2): 280–308. Reutter, K. (1973). [The types of taste buds in fishes. I. Morphological and neurohistochemical investigations on Xiphophorus helleri Heckel (Poeciliidae, Cyprinodontiformes, Teleostei) (author’s transl)]. Z. Zellforsch Mikrosk Anat. 143: 409–423. Reutter, K. (1978). Taste organ in the bullhead (Teleostei). Adv. Anat. Embryol. Cell Biol. 55(1): 3–94. Reutter, K. (1980). SEM- study of the mucus layer on the receptor-field of fish taste buds. In Olfaction and Taste VII, van der Starre, H. (Ed). IRL Press, London, Washington DC, pp. 107. Reutter, K. (1986). Chemoreceptors. In Biology of the Integument, Bereiter-Hahn, J., Matoltsy, A. G. and Richards, K. S. (Eds). Vol. 2, Springer, Berlin, Heidelberg, pp. 586–604. Reutter, K. (1992). Structure of the peripheral gustatory organ, represented by the siluroid fish Plotosus lineatus (Thunberg). In Fish chemoreception, Hara, T. J. (Ed). Chapman & Hall, London, pp. 60–78. Reutter, K., and Witt, M. (1993). Morphology of vertebrate taste organs and their nerve supply. In Mechanisms of taste transduction, Simon, S. A. and Roper, S. D. (Eds). CRC Press, Boca Raton, Ann Arbor, London, Tokyo, pp. 29–82. Reutter, K., and Witt, M. (1999). Comparative aspects of fish taste bud ultrastructure. In Advances in chemical signals in vertebrates, Johnston, E., Müller-Schwarze, D. and Sorensen, P. W. (Eds). Kluwer Academic/Plenum Publishers, New York, Boston, Dordrecht, London, Moscow, pp. 573–581. Reutter, K., and Witt, M. (2004). Are there efferent synapses in fish taste buds? J. Neurocytol. 33(6): 647–656. Riva, A., Loffredo, F., Puxeddu, R., and Testa Riva, F. (1999). A scanning and transmission electron microscope study of the human minor salivary glands. Arch. Oral Biol. 44 Suppl 1: S27–31. Roper, S. D. (1989). The cell biology of vertebrate taste receptors. Annu. Rev. Neurosci. 12: 329–353. Roper, S. D. (2006). Cell communication in taste buds. Cell Mol. Life Sci. 63(13): 1494–1500.
661
Royer, S. M., and Kinnamon, J. C. (1988). Ultrastructure of mouse foliate taste buds: synaptic and nonsynaptic interactions between taste cells and nerve fibers. J. Comp. Neurol. 270: 11–24, 58. Royer, S. M., and Kinnamon, J. C. (1991). HVEM serial-section analysis of rabbit foliate taste buds: I. Type III cells and their synapses. J. Comp. Neurol. 306: 49–72. Ruiz-Avila, L., McLaughlin, S. K., Wildman, D., et al. (1995). Coupling of bitter receptor to phosphodiesterase through transducin in taste receptor cells. Nature 376: 80–85. Saito, I. (1966). Comparative anatomical studies of the oral organs of the poultry. V. Structures and distribution of taste buds of the fowl. (In Japanese). Bull Fac. Agric. Miyazahi. Univ. 13: 95–102. Sbarbati, A., Crescimanno, C., Bernardi, P., and Osculati, F. (1999). Alpha-gustducin-immunoreactive solitary chemosensory cells in the developing chemoreceptorial epithelium of the rat vallate papilla. Chem. Senses 24(5): 469–472. Scalzi, H. A. (1967). The cytoarchitecture of gustatory receptors from the rabbit foliate papillae. Z. Zellforsch Mikrosk Anat. 80(3): 413–435. Schinkele, O. (1942). Über das Vorkommen von Geschmacksknospen im kranialen Drittel des Oesophagus. Z. Mikrosk.-anat. Forsch. 51: 498–501. Schmale, H., Ahlers, C., Blaker, M., et al. (1993). Perireceptor events in taste. Ciba Found Symp. 179: 167–80; discussion 180–185. Schmale, H., and Bamberger, C. (1997). A novel protein with strong homology to the tumor suppressor p53 [In Process Citation]. Oncogene 15(11): 1363–1367. Schmale, H., Holtgreve-Grez, H., and Christiansen, H. (1990). Possible role for salivary gland protein in taste reception indicated by homology to lipophilic-ligand carrier proteins. Nature 343(6256): 366–369. Schulze, F. E. (1863). Über die becherförmigen Organe der Fische. Z. Wiss. Zool. 12: 218–222. Schwalbe, G. A. (1868). Über die Geschmacksorgane der Säugethiere und des Menschen. Arch. Mikr. Anat. 4: 154–187. Schwann, T. (1839). Mikroskopische Untersuchungen über die Übereinstimmung in der Struktur und dem Wachstum der Thiere und Pflanzen. Sander’sche Buchhandlung (Reimer), Berlin. Schwartz, H. G., and Weddell, G. (1938). Observations on the pathways transmitting the sensation of taste. Brain 61: 99–115. Segovia, C., Hutchinson, I., Laing, D. G., and Jinks, A. L. (2002). A quantitative study of fungiform papillae and taste pore density in adults and children. Brain Res. Dev. Brain Res. 138(2): 135–146. Selliseth, N. J., and Selvig, K. A. (1993). Microvasculature of the dorsum of the rat tongue: a scanning electron microscopic study using corrosion casts. Scand J. Dent. Res. 101(6): 391–397. Seta, Y., Oda, M., Kataoka, S., et al. (2011). Mash1 is required for the differentiation of AADC-positive type III cells in mouse taste buds. Dev. Dyn. 240(4): 775–784. Seta, Y., Seta, C., and Barlow, L. A. (2003). Notch-associated gene expression in embryonic and adult taste papillae and taste buds suggests a role in taste cell lineage decisions. J. Comp. Neurol. 464(1): 49–61. Shahbake, M., Hutchinson, I., Laing, D. G., and Jinks, A. L. (2005). Rapid quantitative assessment of fungiform papillae density in the human tongue. Brain Res. 1052(2): 196–201. Shatzman, A. R., and Henkin, R. I. (1981). Gustin concentration changes relative to salivary zinc and taste in humans. Proc. Natl. Acad Sci. U. S. A. 78(6): 3867–3871. Shen, T., Kaya, N., Zhao, F.-L., et al. (2005). Co-expression patterns of the neuropeptides vasoactive intestinal peptide and cholecystokinin with the transduction molecules [alpha]-gustducin and T1R2 in rat taste receptor cells. Neuroscience 130(1): 229–238.
662
Chapter 29
Anatomy of the Tongue and Taste Buds
Siegel, R. E. (1970). Galen on sense perception. His doctrines, observations and experiments on vision, hearing, smell, taste, touch and pain, and their historical sources. S.Karger, Basel, New York.
Toubeau, G., Cotman, C., and Bels, V. (1994). Morphological and kinematic study of the tongue and buccal cavity in the lizard Anguis fragilis (Reptilia:Anguidae). Anat. Rec. 240: 423–433.
Smith, D. V., Akeson, R. A., and Shipley, M. T. (1993). NCAM expression by subsets of taste cells is dependent upon innervation. J. Comp. Neurol. 336: 493–506.
Toyoshima, K., Miyamoto, K., and Shimamura, A. (1987). Fine structure of taste buds in the tongue, palatal mucosa and gill arch of the axolotl, Ambystoma mexicanum. Okajimas Folia Anat. Jpn. 64(2–3): 99–109.
Smith, D. V., Klevitsky, R., Akeson, R. A., and Shipley, M. T. (1994). Expression of the neural cell adhesion molecule (NCAM) and polysialic acid during taste bud degeneration and regeneration. J. Comp. Neurol. 347: 187–196.
Toyoshima, K., Seta, Y., Toyono, T., and Takeda, S. (1999). Merkel cells are responsible for the initiation of taste organ morphogenesis in the frog. J. Comp. Neurol. 406(1): 129–140.
Smith, D. V., Som, J., Boughter, J. D., Jr,., et al. (1999). Cellular expression of alpha-gustducin and the A blood group antigen in rat fungiform taste buds cross-reinnervated by the IXth nerve. J. Comp. Neurol. 409(1): 118–130. Sobotta, J. (1993). Atlas der Anatomie des Menschen. Vol.1. Urban und Schwarzenberg, München. Sömmering, S. T. (1806). Abbildungen der menschlichen Organe des Geschmackes und der Stimme. Varrentrapp und Wenner, Frankfurt. Spielman, A. I. (1990). Interaction of saliva and taste. J. Dent. Res. 69(3): 838–843. Sprissler, C. (1994). Ultrastruktur der Geschmacksknospe der japanischen Wachtel (Coturnix coturnix japonica). University of Tübingen. Srur, E., Stachs, O., Guthoff, R., et al. (2010). Change of the human taste bud volume over time. Auris. Nasus. Larynx. 37(4): 449–455. Starostik, M. R., Rebello, M. R., Cotter, K. A., et al. (2010). Expression of GABAergic receptors in mouse taste receptor cells. PLoS One 5(10): e13639. Stone, L. M., Finger, T. E., Tam, P. P., and Tan, S. S. (1995). Taste receptor cells arise from local epithelium, not neurogenic ectoderm. Proc. Natl. Acad. Sci. U.S.A. 92: 1916–1920. Stone, L. S. (1940). The origin and development of taste organs in salamanders observed in the living condition. J. Exp. Zool. 83: 481–506.
Toyoshima, K., and Shimamura, A. (1987). Monoamine-containing basal cells in the taste buds of the newt Triturus pyrrhogaster. Arch. Oral Biol. 32: 619–621. Toyoshima, K., and Tandler, B. (1987). Modified smooth endoplasmic reticulum in type II cells of rabbit taste buds. J. Submicrosc. Cytol. 19: 85–92. Tuckerman, F. (1889). On the development of the taste-organs of man. J. Anat. Physiol. 23: 559–582. Uchida, T. (1980). Ultrastructural and histochemical studies on the taste buds in some reptiles. Arch. Histol. Jpn. 43: 459–478. Ueda, K., Ichimori, Y., Okada, H., et al. (2006). Immunolocalization of SNARE proteins in both type II and type III cells of rat taste buds. Arch. Histol. Cytol. 69(4): 289–296. Vandenbeuch, A., Clapp, T. R., and Kinnamon, S. C. (2008). Amiloride-sensitive channels in type I fungiform taste cells in mouse. BMC Neurosci. 9: 1. Varatharasan, N., Croll, R. P., and Franz-Odendaal, T. (2009). Taste bud development and patterning in sighted and blind morphs of Astyanax mexicanus. Dev. Dyn. 238(12): 3056–3064. Verson, E. (1868). Beiträge zur Kenntnis des Kehlkopfes und der Trachea. Sitzungsber. Wiener Acad. Wissenschaft, Math.-naturwiss.Klasse 57: 1093–1102. von Düring, M. V., and Andres, K. H. (1976). The ultrastructure of taste and touch receptors of the frog’s taste organ. Cell Tissue Res. 165(2): 185–198.
Stornelli, M. R., Lossi, L., and Giannessi, E. (2000). Localization, morphology and ultrastructure of taste buds in the domestic duck (Cairina moschata domestica L.) oral cavity. Ital. J. Anat. Embryol. 105(3): 179–188.
von Vintschgau, M., and Hönigschmied, J. (1877). Nervus glossopharyngeus und Schmeckbecher. Arch. Physiol. 14: 443–448.
Suzuki, Y., Takeda, M., Obara, N., and Nagai, Y. (1996). Phagocytic cells in the taste buds of rat circumvallate papillae after denervation. Chem. Senses 21(4): 467–476.
Wagner, R. (1837). Bestätigung des Panizzaschen Lehrsatzes, dass das 9te Nervenpaar (n.glossopharyngeus) der Geschmacksnerv ist. Frorieps Notizen 4: 129–131.
Svejda, J., and Janota, M. (1974). Scanning electron microscopy of the papillae foliatae of the human tongue. Oral Surg. Oral Med. Oral Pathol. 37(2): 208–216.
Wakisaka, S., Tabata, M. J., Maeda, T., et al. (1998). Immunohistochemical localization of pleiotrophin and midkine in the lingual epithelium of the adult rat. Arch. Histol. Cytol. 61(5): 475–480.
Tandler, B., Pinkstaff, C. A., and Riva, A. (1994). Ultrastructure and histochemistry of human anterior lingual salivary glands (glands of Blandin and Nuhn). Anat. Rec. 240: 167–177.
Waller, A. (1847). Microscopic examination of the papillae and nerves of the tongue of the frog, with observations on the mechanism of taste. London, Edinburgh, and Dublin Philosoph. Magazine J. Sci. Vol XXX: 277–289.
Thirumangalathu, S., Harlow, D. E., Driskell, A. L., et al. (2009). Fate mapping of mammalian embryonic taste bud progenitors. Development 136(9): 1519–1528. Tizzano, M., Cristofoletti, M., Sbarbati, A., and Finger, T. E. (2011). Expression of taste receptors in solitary chemosensory cells of rodent airways. BMC Pulm. Med. 11: 3. Tomchik, S. M., Berg, S., Kim, J. W., et al. (2007). Breadth of Tuning and Taste Coding in Mammalian Taste Buds. J. Neurosci. 27(40): 10840–10848. Tomonari, H., Miura, H., Nakayama, A., et al. (2012). Gα−gustducin Is Extensively Coexpressed with Sweet and Bitter Taste Receptors in both the Soft Palate and Fungiform Papillae but Has a Different Functional Significance. Chemical Senses 37(3): 241–251. Toto, P. D., Nadimi, H., and Martinez, R. (1993). von Ebner’s gland. an immunohistochemical study. Ann. N. Y. Acad. Sci. 694: 322–324.
Waller, A. (1849). Minute structure of the papillae and nerves of the tongue of the frog and the toad. Communicated by R. Owen. Philosoph.Transact.Royal Soc.London Pt.I: 139–149. Welsch, U., and Storch, V. (1969). [Fine structure of the taste buds of catfish (Clarias batrachus (L) and Kryptopterus bicirrhis (Cuvier and Valenciennes)]. Z. Zellforsch Mikrosk. Anat. 100(4): 552–559. Whitear, M. (1970). The skin surface of bony fishes. J.Zool.London 160: 437–454. Whitear, M. (1992). Solitary chemosensory cells. In Fish chemoreception, Hara, T. (Ed). Chapman & Hall, London, pp. 103–125. Whitehead, M. C., Ganchrow, J. R., Ganchrow, D., and Yao, B. (1998). Neural cell adhesion molecule, neuron-specific enolase and calcitonin gene-related peptide immunoreactivity in hamster taste buds after chorda tympani lingual nerve denervation. Neuroscience 83(3): 843–856.
References Williams, P. L., Warwick, R., Dyson, M., and Bannister, L. H. (1989). Gray’s Anatomy. Curchill Livingstone, Edinburgh London. Wilson, J. G. (1905). The structure and function of the taste-buds of the larynx. Brain 28: 339–351. Witt, M. (1993). Ultrastructure of the taste disc in the red-bellied toad Bombina orientalis (Discoglossidae, Salientia). Cell Tissue Res. 272: 59–70. Witt, M. (1995). Distribution of vasoactive intestinal peptide-like immunoreactivity in the taste organs of teleost fish and frog. Histochem. J. 27: 161–165. Witt, M. (1996). Carbohydrate histochemistry of vertebrate taste organs. Progr. Histochem. Cytochem. 30/4: 1–172. Witt, M., and Kasper, M. (1998). Immunohistochemical distribution of CD44 and some of its isoforms during human taste bud development. Histochem. Cell Biol. 110: 95–113. Witt, M., and Kasper, M. (1999). Distribution of cytokeratin filaments and vimentin in developing human taste buds. Anat. Embryol. 199: 291–299. Witt, M., and Miller, I. J., Jr., (1992). Comparative lectin histochemistry on taste buds in foliate, circumvallate and fungiform papillae of the rabbit tongue. Histochemistry 98(3): 173–182. Witt, M., and Reutter, K. (1988). Lectin histochemistry on mucous substances of the taste buds and adjacent epithelia of different vertebrates. Histochemistry 88: 453–461. Witt, M., and Reutter, K. (1990). Electron microscopic demonstration of lectin binding sites in the taste buds of the European catfish Silurus glanis (Teleostei). Histochemistry 94: 617–628. Witt, M., and Reutter, K. (1996). Embryonic and early fetal development of human taste buds: a transmission electron microscopical study. Anat. Rec. 246(4): 507–523. Witt, M., and Reutter, K. (1997). Scanning electron microscopical studies of developing gustatory papillae in humans. Chem. Senses 22: 601–612. Wong, G. T., Ruiz-Avila, L., Ming, D., et al. (1996). Biochemical and transgenic analysis of gustducin’s role in bitter and sweet transduction. Cold Spring Harb. Symp. Quant. Biol. 61: 173–184. Wyss, H. v. (1870). Die becherförmigen Organe der Zunge. Arch. mikrosk. Anat. 6: 237–260. Yamasaki, F., and Takahashi, K. (1982). A description of the times of appearance and regression of marginal lingual papillae in human fetuses and newborns. Anat.Rec. 204: 171–173.
663
Yang, R., Crowley, H. H., Rock, M. E., and Kinnamon, J. C. (2000). Taste cells with synapses in rat circumvallate papillae display SNAP-25-like immunoreactivity. J. Comp. Neurol. 424(2): 205–215. Yee, C., Bartel, D. L., and Finger, T. E. (2005). Effects of glossopharyngeal nerve section on the expression of neurotrophins and their receptors in lingual taste buds of adult mice. J. Comp. Neurol. 490(4): 371–390. Yee, C. L., Yang, R., Böttger, B., et al. (2001). “Type III” cells of rat taste buds: immunohistochemical and ultrastructural studies of neuron-specific enolase, protein gene product 9.5, and serotonin. J. Comp. Neurol. 440(1): 97–108. Yoshie, S., Wakasugi, C., Teraki, Y., et al. (1988). Immunocytochemical localizations of neuron-specific proteins in the taste bud of the guinea pig. Arch. Histol. Cytol. 51: 379–384. Zachar, P. C., and Jonz, M. G. (2011). Confocal imaging of Merkel–like basal cells in the taste buds of zebrafish. Acta Histochem. 114(2): 101–115. Zancanaro, C., Sbarbati, A., Bolner, A., et al. (1995). Biogenic amines in the taste organ. Chem.Senses 20: 329–335. Zhang, C., and Oakley, B. (1996). The distribution and origin of keratin 20-containing taste buds in rat and human. Differentiation 61(2): 121–127. Zhang, C. X., Cotter, M., Lawton, A., et al. (1995). Keratin 18 is associated with a subset of older taste cells in the rat. Differentiation 59: 155–162. Zhao, F. L., Shen, T., Kaya, N., et al. (2005). Expression, physiological action, and coexpression patterns of neuropeptide Y in rat taste-bud cells. Proc. Natl. Acad. Sci. U.S.A. 102(31): 11100–11105. Zimmermann, K. W. (1927). Die Speicheldrüsen der Mundhöhle und die Bauchspeicheldrüse. In Handbuch der Mikroskopischen Anatomie des Menschen, Möllendorf, W. v. (Ed). Vol. V, Part 1, Springer, Berlin, pp. 61–244. ˙ Zuwała, K. (1997). Ultrastructure of premetamorphic taste organs of the Bombina variegata. Rocz. Akad. Med. Bialymst. 42 Suppl 2: 204–207. ˙ Zuwała, K., and Jakubowski, M. (1991). Development of taste organs in Rana temporaria. Transmission and scanning electron microscopic study. Anat. Embryol. (Berl) 184(4): 363–369.