1. Explain the four general types of guidance cues that guide neuronal growth cones. Describe specific examples that illustrate the role of each of these cues in vivo. Some guidance cues are clearly evolutionarily conserved, such as netrins in vertebrates and nematodes. Explain. What is the 'labeled pathways hypothesis?'
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 these? 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. 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.
4. 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?
5. "The mechanisms of apoptosis are very highly conserved -- they have the hallmark of a common, fundamental biochemical process found in all animal cells." 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.
6. 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. What do we mean by saying that cancer is a 'multiple hit' phenomenon?
7. 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.
8. 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?
9. (Overlapping question with 8, viewed somewhat differently). 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.)
10. Wnt signaling can function in a variety of ways in C. elegans - describe canononical wnt signaling in C. elegans vulval development and non-canonical (atypical) wnt signaling in the specification of endoderm. What are the three distinct beta-catenins in C. elegans and how do they function similarly or differently from beta-catenin in mammals? Which members of the Wnt signaling pathway in humans are proto-oncogenes and which are tumor suppressor genes (and why)?
11. Describe the basic mechanism of chromosomal sex determination in mammals, flies and bees. Explain an example of environmental sex determination. What tissue is responsible for primary sex determination in mammals? How are secondary sex characteristics determined? Describe the basic molecular players in mammalian sex determination, and how they are believed to function. What kinds of observations of atypical individuals aided in identifying the SRY and DAX1 genes (for example)? How may mammalian and fly sex determination genes be functioning similarly?
12. Explain the importance of modularity in the evolution of development. What are some examples of developmental modules? Explain three processes that can alter development by altering modules: dissociation, duplication & divergence, co-option. Explain temporal dissociation (heterochrony) and spatial dissociation (allometry). What is neotony? [Note that pp 581-583 (Gilbert) discuss forms of heterochrony, including neoteny as seen in the axolotl.]