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Unveiling the Mysteries of Morphogenesis: Development, Growth, and Differentiation

Explore five major questions of morphogenesis, from tissue formation to organ construction and achieving polarity. Delve into the role of differential adhesion and signaling in morphogenesis, along with steps in developing L-R asymmetry. Examine human embryology, disease development, and clinical correlations for a comprehensive understanding of organogenesis.

benjamin-stewart
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Unveiling the Mysteries of Morphogenesis: Development, Growth, and Differentiation

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  1. Five Major Questions of Morphogenesis: • 1. How are tissues formed from populations of cells? • e.g. how do neural retinal cells stick to each other and not the retinal pigmented epithelium? • 2. How are organs constructed from tissues? • e.g. the retina must be positioned properly relative to other structures to function properly. • 3. How do organs form in particular locations, and how do migrating cells reach the • appropriate home? • e.g. What stops an eye from forming somewhere else? How do cells like pigment cells know where and how to move? • 4. How do organs and their cells grow in a coordinated manner throughout development? • e.g. How do all of the cell types and tissues that make up the eye grow to make each structure exactly the appropriate size and shape needed to make a functional eye? • 5. How do organs achieve polarity? • e.g. The finger and the forearm use the same cell types, but their positioning is different. How does that happen?

  2. A Role for Differential Adhesion

  3. Inappropriate changes in adhesion are a hallmark of metastasis

  4. Three Fundamental Types of adhesion systems Cell junctional molecules Cell adhesion molecules Substrate adhesion molecules

  5. Cell adhesion molecules. A, B: As actin is bound to the cadherins at the level of the desmosomes, its contraction causes the apex of the sheath of cells to constrict, as the basement membrane is not elastic. Such a constriction contributes to the formation of the neural groove. C: The cell at the migration front sends out projections to feel the extracellular membrane for molecules for which their integrins have an affinity. Once such molecules are found, they are bound and used as anchors to allow actin to pull the cell in that direction. Adjacent cells are dragged by the leading cells through CAM binding.

  6. Using Signaling to coordinate differentiation and morphogenesis

  7. There are multiple ways to signal

  8. Some General Types of Signals

  9. Growth factors and mitogens often use receptor tyrosine kinases

  10. Many early embryonic signals go through BMPs (TGF--like proteins)

  11. TGF- family members affect many systems

  12. Wnt signaling

  13. Hedgehog isoforms are used over and over during development

  14. Notch/Delta is an example of lateral signaling

  15. Steps in developing L-R asymmetry • Establishment of asymmetry • Step 1 - breaking symmetry • Step 2 - transfer of left-right positional information to the lateral plate mesoderm B. Propagation and maintenance of L-R asymmetry • Step 3 - stabilization of side-specific gene expression • Step 4 - creation of a barrier across the midline • Step 5 - asymmetric growth of organs C. Wright, 2001. Dev. Cell 1, 179-186

  16. There really are reasons to care (beyond it being really cool stuff)

  17. Mice homozygous mutant for Lim-1 for no head structures

  18. MEDI 510 (IBS 518) July 24 - August 7, 2006 Human Embryology: Development and Disease Charles Saxe, Ph.D., Course Director Text: Moore, K.W., The Developing Human, W.B. Saunders Co., 7th ed., 2003 Place: Week 1 : lectures and clinical cor relations will be in Whitehead Auditorium Week 2: lectures and clinical correlations will be in the WHSCAB Auditorium Exams: all exams will be in the WHSCAB Auditorium Day Date Time Event Speaker Title Mon 7/24 9:00a Lect 1 Dr. Saxe Basic mechanisms of differentiation 11:00 Lect 2 Dr. Saxe Morphogenesis and cell interactions 11:45p Corr K. Torrente Intro to information retrieval at Emory Tues 7/25 9:00 Lect 3 Dr. Saxe Principles of teratogenesis 11:00 Lect 4 Dr. Saxe Gametogenesis and fertilization 1:00p Clin Corr Dr. Mitchell Advances in in vitro fertilization Wed 7/26 9:00 Clin Corr Ms Kinlaw Neonatal ethics 10:30 Lect 5 Dr. Saxe Extra - embryoni c membranes; placenta 1:00p Lect 6 Dr. Saxe Urogenital system I. Gonads Thur 7/27 9:00 Lect 7 Dr. Saxe Urogenital system II. Renal development 11:00 Clin Corr Dr. Smith Anomalies of the urinary tracts Fri 7/28 9:00 Lect 8 Dr. Moberg Ectoderm - neurulation; CNS formation 10:45 Clin Corr Dr. Sladky Congenital Neural defects ================================================================================== Mon 7/31 9:00 MIDTERM (1 hr) Tues 8/1 9:00 Lect 9 Dr. Saxe Cardiovasc I. Heart,CV system Septation 10:30 Lect 10 Dr. Saxe Cardiovasc II. Congenital heart defects 11:30 Clin Corr Dr.Sutherland Common congenital heart defects Wed 8/2 9:00 Lect 11 Dr. Saxe Mesoderm I. limb and muscle; mitotic mechanisms 10:30 Lect 12 Dr. Saxe Mesoderm II. Limb and skeletal formation 1:00p Clin Corr Dr. Weil Congenital limb anomalies Thur 8/3 9:00 Lect 13 Dr. Saxe Endoderm I. Respiratory system 10:30 Lect 14 Dr. Saxe Endoderm II. Gut, Liver, Pancreas 1:00p Clin Corr Drs Nasr and Anomalies of the gut Williams Fri 8/4 9:00 Lect 15 Dr. Saxe Cancer: Developmental mecha nisms in oncogenesis Mon 8/7 9:00 FINAL EXAM (2 hr)

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