Molecular Regulation (Embryology) PDF

WE MAKE DOCTORS WEEK 3 TO 8: MOLECULAR REGULATION DR. GUADALUPE RODRIGUEZ EMBRYOLOGY OBJECTIVES: Identify the main transcription factors that participate in the regulation of the trilaminar layers derivatives (type and function) Identify the main Growth factors that participate in the regulation...

WE MAKE DOCTORS WEEK 3 TO 8: MOLECULAR REGULATION DR. GUADALUPE RODRIGUEZ EMBRYOLOGY OBJECTIVES: Identify the main transcription factors that participate in the regulation of the trilaminar layers derivatives (type and function) Identify the main Growth factors that participate in the regulation of the trilaminar layers derivatives (type and function). Ectodermal Germ Layer Ectodermal germ layer The ectodermal germ layer gives rise to the organs and structures that maintain contact with the outside world: The central nervous system The peripheral nervous system The sensory epithelium of the ear, nose, and eye The epidermis, including the hair and nails In addition, it gives rise to the following: The subcutaneous glands The mammary glands The pituitary gland Enamel of the teeth Molecular regulation of neural induction Upregulation of fibroblast growth factor (FGF) signaling Inhibition of growth factor bone morphogenetic protein 4 (BMP4) If ectoderm is protected from exposure to BMPs, its “default state” is to become neural tissue. In the cranial region (forebrain and midbrain tissues), inactivation of BMPs is caused by noggin, chordin, and follistatin These act on forebrain adn midbrain tissues In the hindbrain and spinal cord regions, inactivation of BMPs is effected by WNT3 and FGF. The fate of the entire ectodermal germ layer depends on BMP concentrations: HIGH levels induce epidermis formation and mesoderm to ventralize to form intermediate and lateral plate mesoderm INTERMEDIATE levels, at the border of the neural plate and surface ectoderm, induce the neural crest LOW concentrations cause formation of neural ectoderm. BMPs and FGFs regulate NCC (neural crest cells) migration, proliferation, and differentiation. Abnormal concentrations of these proteins have been associated with neural crest defects in the craniofacial region. Molecular regulation of neural crest induction Induction of NCC requires an interaction at the border of the neural plate and surface ectoderm (epidermis). Intermediate concentrations of BMPs are established at this boundary compared to neural plate cells. These concentrations together with FGF and WNT proteins, induce PAX3 and other transcription factors that “specify” the neural plate border. In turn, these transcription factors induce a second wave of transcription factors, including SNAIL and FOXD3, which specify cells as neural crest, and SLUG, which promotes crest cell migration from the neuroectoderm. Mesodermal Germ Layer Mesodermal germ layer The mesodermal germ layer gives rise to: Muscle tissue Cartilage and bone Dermis of the skin Vascular system Urogenital system Spleen Cortex of the suprarenal glands Molecular regulation of somite formation Formation of somites from unsegmented presomitic (paraxial) mesoderm depends on a segmentation clock established by cyclic expression of the genes of the NOTCH and WNT signaling pathways that are expressed in presomitic mesoderm. NOTCH PROTEIN Accumulates in presomitic mesoderm destined to form the next somite and then decreases as that somite is established. Boundaries for each somite are regulated by retinoic acid (RA) and a combination of FGF8 and WNT3a. RA is expressed at high concentrations cranially and decreases in concentration caudally, whereas the combination of FGF8 and WNT3a proteins is expressed at higher concentrations caudally and lower ones cranially. Molecular regulation of somite differentiation Signals for somite differentiation are derived from the notochord, neural tube, epidermis, and lateral plate mesoderm. The notochord and floor plate of the neural tube secrete SHH (Sonic Hedgehog) and Noggin, induce the ventromedial portion of the somite to become sclerotome. Sclerotome cells express the transcription factor PAX1, which initiates the cascade of cartilage and bone-forming genes for vertebral formation. Expression of PAX3, regulated by WNT proteins from the dorsal neural tube, marks the dermomyotome region of the somite. WNT proteins from the dorsal neural tube also target the dorsal midportion of the somite, causing it to initiate expression of the muscle specific gene MYF5 and MYOD to form muscle precursors. The midportion of the dorsal epithelium of the somite is directed by neurotrophin 3 (NT-3), secreted by the dorsal neural tube, to form dermis. Molecular regulation of blood vessel formation FGF2 induces blood island development from competent mesoderm cells that form hemangioblasts. Hemangioblasts are directed to form blood cells and vessels by vascular endothelial growth factor (VEGF), which is secreted by surrounding mesoderm cells. Hemangioblasts in the center of blood islands form hematopoietic stem cells, the precursors of all blood cells. Peripheral hemangioblasts differentiate into angioblasts that proliferate and are eventually induced to form endothelial cells by VEGF secreted by surrounding mesoderm cells.  Once the process of vasculogenesis establishes a primary vascular bed, which includes the dorsal aorta and cardinal veins, additional vasculature is added by angiogenesis, the sprouting of new vessels. This process is also mediated by VEGF, which stimulates proliferation of endothelial cells at points where new vessels are to be formed. Maturation and modeling of the vasculature are regulated by other growth factors, including platelet-derived growth factor (PDGF) and TGF- B, until the adult pattern is established. Endodermal Germ Layer  Endodermal germ layer During development, endoderm gives rise to the following: The epithelial lining of the respiratory tract The parenchyma of the thyroid, parathyroids, liver, and pancreas The reticular stroma of the tonsils and the thymus The epithelial lining of the urinary bladder and the urethra The epithelial lining of the tympanic cavity and auditory tube  Patterning of the AP axis Craniocaudal patterning of the embryonic axis is controlled by the homeobox genes that are arranged in four clusters—HOXA, HOXB, HOXC, and HOXD. Genes toward the 3’ end of the chromosome control development of more cranial structures; those more toward the 5’ end regulate differentiation of more posterior structures. Together, they regulate the axis of the embryo on all 3 germ layers. References: Chapter 6. Third to Eight Weeks: The Embryonic Period Bevis, R. (1992). Langman’s Medical Embryology, 6th edition T W Sadler Langman’s Medical Embryology, 6th Edition Williams & Wilkins 412pp £20.50 0-683- 07473-8. Nursing Children and Young People, 4(3), 14. https://doi.org/10.7748/paed.4.3.14.s14 Thank You!