Bilaminar embryo Initially, Initially, all the energy is from the zygote. But as the zygote needs more energy, it implants into the endometrium. Implantation takes places on day 6. The only reason implantation can take place is because of tissue specialization. Trophoblast -> placenta Inner cell mass -> fetus Providers of energy (Trophoblast focuses on the acquisition of energy from the mother) 1. Lungs -> provide oxygen 2. GI tract -> absorb nutrients and energy substrates 3. Liver -> stores and generates energy
Tissues that establish order (inner cell mass) 1. Endocrine system -> regulate biochemical processes 2. Bones, skin, connective tissue -> physical shape and structure 3. Brain and nervous system -> control and integrate function of the body
After implantation, the the trophoblast forms the chorion, which grows finger like projections called villi. These chrionic villi grow into the endometrium and become the fetal component of the placenta. The maternal component is called the decidua basalis. There is a thin layer of amnion that contains the amniotic fluid and a yolk sac that serves as the secondary source of energy and non-specialized stem cells .
Week 2: 2 layered structure (epiblast and hypoblast) Week 3: 3 layered structure (ectoderm, mesoderm and endoderm -> also called a gastrula)
Neurulation -> formation of the neural tube Neural tube and neural crest are derived from the ectoderm, but it is the notochord and the mesoderm that make it happen.
Neural crest derivatives
Malleus, incus and stapes
Chromaffin cells make up the catechcolamines (Epi and NE)
Neuroectoderm: • Brain and spinal cord • Oligodendrocytes • Astrocytes • Ependymal cells • Optic nerve • Retina • Pineal glands • Posterior pituitary
Endoderm • GI tract (esophagus to pectinate line) • Liver, gallbladder, pancreas • Lungs • Thymus • Parathyroid gland • Follicular cells of thyroid • Epithelium of bladder/urethra • Lower 2/3 of vagina Most of the bladder and the urethra are derived from the mesoderm along with the rest of the urinary system but bladder epithelium and urethra epithelium are derived from endoderm
Surface ectoderm: ectodermal tissue that did not become neurological because it did not get influenced by the notochord • Lenses of eye • Olfactory epithelium • Inner ear • Anterior pituitary • Oral epithelium • Salivary glands • Epidermis • Sweat glands • Mammary glands • Anal canal distal to the pectinate line. line. Both extreme ends of the GI tract come of the ectoderm (oral epithelium and the distal part of the anal canal)
Mesoderm: provides most of the connective tissues (support) • Bone, muscle, bone marrow, blood cells, heart, blood vessels, lymphatics • Upper portion of the vagina • Kidneys, adrenal cortex • Gonads • Dermis of skin
Teratogenesis -> embryology gone wrong Weeks 3-8: organogenesis organogenesis Week 4: 4 limbs, limbs, 4 chambered heart Week 8: fetal fetal movement (eight gait) Week 10: 10: genitalia takes shape (ten -> penis) These days are measured from the day of conception (developmental age)
Teratogenic drugs:
Fluoroquinolone -> cartilage damage Methotrexate -> inhibits folate metabolism leading to neural tube defects/abortion Statin -> CNS and limb abnormalities Isotretinoin -> retinoic acid drug that can cause spontaneous abortions. Excess Vitamin A can interfere with neural crest cell migration and HOMEOBOX gene expression
Heparin (anti-coagulant) is considered safe during pregnancy!
Category X Drugs: • Methotrexate • Statins • Warfarin • Isotretinoin • Diethylstillbestrol Diethylstillbestrol (DES) • Thalidomide
Procedures and conditions: • Ionizing radiation • Excessive Vitamin A -> interferes with neural crest cell migration • Maternal diabetes -> this doesn't include gestational diabetes. • Iodine deficiency -> baby can be born with congenital hypothyroidism, hypothyroidism, which is called cretinism. In this case it's not eh iodine that is teratogenic, instead the iodine deficiency that causes the problems. • Cocaine, tobacco -> interfere with blood circulation to the fetus and can cause growth restriction • Alcohol Fetal alcohol syndrome is the number one cause of intellectual disability in the US. Microencephaly Holoprosencephaly -> hemispheres fail to separate along the mid line, leading to facial anomalies !
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Embryogenesis Homeobox (HOX) gene: • Blueprint of skeletal morphology • Code for transcription regulators • Mutation in Homeobox HOXD-13 -> synpolydactly • Retinoic acid (Vitamin A) alters HOX gene expression Sonic Hedgehog Gene: • It is expressed at the buds of the limbs in the zone called the ZPA (Zone of Polarizing Activity) • Important in organizing the layout of the embryo in the anterior to posterior direction, setting up which pole is going to become the head and which is going going to become the tail. • Mutation can cause holoprosencephaly WNT7 Gene: • Important for organizing the embryo along the dorsal-ventral axis (feet and nose pointing in the same direction) FGF Gene • Fibroblast growth factor -> important for limb lengthening • Defect -> short limbs • Defect in FGFR3 -> achondroplasia (short limbs) Rapid Fire Facts • Most common cause of neutral tube defects -> folate deficiency • Most common cause of congenital malformations in the US -> alcohol use during pregnancy • Most common cause of intellectual disability in the U.S. -> fetal alcohol syndrome
Organelles 1. Nuclear localization signals A. Amino acid sequences that are rich in lysine, arginine arginine and proline (because these are positively charged, charged, they bind easily to the negatively charged DNA) B. Essential component of the proteins bound for or residing in the nucleus C. Nuclear pores recognize these signals and transport proteins into the nucleus via ATPase 2. Cell cycle A. Hepatocytes and lymphocytes can go from Go to G1 phase and being the cell cycle if needed B. Bone marrow stem cells are designed to divide ver y rapidly. a. These cells never go into Go. C. Phases a. Go b. G1: c. S d. G2: e. M phase: mitosis D. To control the cells division, there are check points that control transfer between these phases a. Very highly highly regulated process b. Tumor suppressor proteins 1. Rb Gene: between G1 and S phase (Retinoblastoma and Osteosarcoma) 2. p53 3. Mutation in these genes result in unregulated growth. c. Cyclins 1. Regulatory proteins that control cell cycle events 2. Activate CDKs d. Cyclin-depending kinases (CDK) 1. Uses ATP to phosphorylase things (add phosphate to things) 2. Must be activated
