2. (Overlapping question with 1, viewed somewhat differently) Migration of growth cones and neural crest cells (or any cell type, for that matter) depends on interactions with other cells or with the extracellular matrix (ECM). Cell surface proteins (usually transmembrane proteins) that mediate this interactions fall into two general classes: CAMs and ECM receptors. What are the major classes of such proteins? Give an example of a specific CAM and an ECM receptor that acts to guide the migration of growth cones or neural crest cells during nervous system development.
3. Cell adhesion can have different effects in migration and guidance depending on the relative strength of adhesion. Describe an example of a situation in which the same molecule can both promote or inhbit migration by changes in cell adhesion.
4. Growth factors, neurotrophins, and signaling proteins can play multiple roles during development: as survival factors regulating apoptosis, chemoattractant factors for growth cones, instructive factors specifying the fates of cells. Describe at least one example of each of these three roles played such diffusible proteins.
5. What are some of the 'uses' of programmed cell death/apoptosis? Cell death is prominent in neural development in both invertebrates and vertebrates, although there seem to be differences in how cells are specified to die (or live). What is some of the evidence in the vertebrates (for example, among motor neurons of the spinal cord) that cell-cell interactions are important in determining which cells live or die?
6. ÒThe mechanisms of apoptosis are very highly conserved -- they have the hallmark of a common, fundamental biochemical process found in all animal cells.Ó Explain the meaning of this statement by describing what you know about the molecular mechanisms of apoptosis and various experiments in mammals and worms that have lead to our current understanding of the process.
7. How is caspase function in apoptosis different and more complicated in mammals than in C. elegans? In what other ways is regulation of apoptosis/PCD more complex in mammals?
8. How can an abnormal growth factor receptor can cause cancer? What other kinds of normal cellular genes are proto-oncogenes? (And why are they proto-oncogenes?) How can an alteration in the function of p53 or other tumor suppressor gene lead to cancer? Explain the role(s) of cell cycle regulators as tumor suppressor genes. Define the terms proto-oncogene, oncogene, and tumor suppressor gene, and explain how the normal function of a given gene determines which it is (or can become). What do we mean by saying that cancer is a Òmultiple hitÓ phenomenon?
9. How are levels of P53 protein regulated by MDM2 and p14-ARF? Explain how Myc overexpression can lead to apoptosis, and what must happen in a potentially cancerous cell to escape apoptosis triggered by P53? How does the retinoblastoma protein (pRB or RB) regulate the cell cycle? How do p16-INK4a and CyclinD/cdk4 function to alter pRB function and regulate progression through the cell cycle? Which of these genes (typically) function as tumor suppressors, and which as proto-oncogenes?
10. We have seen the action of Wnt signaling pathways in many different tissues and organisms. Compare and contrast the Wnt signaling pathways in at least two different developmental systems. Which Wnt pathways are ÒcanonicalÓ vs. Ònon-canonical?Ó How can Wnt signaling play a role in oncogenesis (and which genes in the pathway are proto-oncogenes vs. tumor suppressor genes)?
11. Explain what is meant by the terms "autonomous specification" versus "conditional specification" in development. Give examples of observations and experiments that demonstrate these two modes of development. Describe a specific example in which the molecular basis of autonomous specification is known. Both conditional and autonomous specification can be seen in C. elegans early development (controlled by maternal genes such as skn-1, pie-1, mom-2, mom-5, pop-1, etc.) - explain examples of each in determination of early blastomere fate.
12. Describe the inductive process that leads to vulval formation in C. elegans and some of the experiments that demonstrated these cell-cell interactions. What kinds of proteins are involved in the signaling and reception between the cells involved? How does the control of vulval development in C. elegans parallel the control of mammalian epidermal cell proliferation?
13. (Overlapping question with 11 and 12). We have examined a number of different developmental systems in which homologous molecular signaling pathways are used to execute different cell-cell interactions and cell fate decisions. Compare and contrast one of these pathways in two different organisms/cell fate decisions (e.g., RTK pathways in worm and mammal; Wnt pathway in worm, amphibian and mammal; Hedgehog pathway; etc.)
14. Explain how modularity (both structural and molecular) is important in evolution of developmental mechnanisms via dissociation. Explain the concept of heterochronic dissociation via neoteny, including examples of neotenic organims. What is the phylotypic stage of the vertebrate, and what does it tell us about the evolution of developmental mechanisms?