Part1:
1. Name three properties of a tissue-specific stem cell; for each property, describe an experiment that would demonstrate a cell
has that property. (30 points)
2. Draw a proposed lineage tree for a neural stem cell during embryonic brain development. How would you predict that this tree
would differ in primates? Draw a version of your tree for a gyrencephalic species. (30 points)
3. Imagine that you have identified a novel gene, Frisby, which is uniquely expressed in humans during neural development and
which causes small gyri to form when you introduce it into a region of the mouse cortex. Propose a function for this gene and explain
how you would test this function. (40 points)
Part 2:
In the nematode, C. elegans, UNC-6/Netrin is expressed in ventrally located cells and the SLT-1, nematode homolog of slit, is expressed
in muscle cells on the dorsal side. AVM touch neurons normally extend axonal processes toward the ventral side. In unc-6 or unc-40
mutants, AVM axons frequently fail to reach the ventral side but turn and grow along the anterior/posterior axis. As indicated in the
table below, however, this effect is incomplete; some AVM axons show normal ventral outgrowth in either unc-6 or unc-40 mutants.
Genotype % Defective PVM axons
unc-40/unc-40 62%
unc-6/unc-6 65%
Based on your knowledge of axonal guidance cues:
(A) Suggest a likely explanation for the incomplete penetrance of the AVM axon outgrowth defect in unc-6 and unc-40 mutants.
(B) Suggest at least one experiment to test your model.
Part 3:
Length limit 1 Page, 1.5 Spacing, 12 Pt Font
We discussed diffusible and membrane trans-synaptic signals inducing synaptogenesis at the NMJ (neuromuscular junction) Propose a
hypothesis explaining why both signal classes might be required at a single synapse.
From only the Drosophila NMJ, order *all* known trans-synaptic signals in your proposed hypothesis, ascribing non-overlapping roles to
each signal.
Points will be awarded based on; 1) how clever and well supported your hypothesis is, and 2) complete, correct and detailed information
supporting your proposed signal roles.
list ALL drosophila NMJ trans-synaptic signals, not just those directly related to your proposed hypothesis. This should be a short
list.
Carter Question
Please limit your answer to a maximum of 1 single-spaced, 11pt font, 1 inch margin, page.
In the paper on mature BDNF vs proBDNF in synapse competition by Je et al., PNAS, 109:15924-9. The authors suggest that mature BDNF
promotes synapse stabilization.
1) Suggest one general mechanism to explain how BDNF might stabilize a synapse. In your explanation, state one specific hypothesis
that you could experimentally test.
2) Describe one experiment to test your hypothesis.
3) You decide to perform a similar experiment with mammalian cells, using rat neurons and muscle cells. Similar to the Xenopus
results (Fig.1 of Je et al.), you find that the activated synapse is stablilized, but the inactive one withdraws. Moreover, you find
that adding a pan-matrix metalloprotease (MMP) inhibitor induces the retraction of both axons, even the active one (similar to Fig. 4
of Je et al.). You also find that there is no retraction of the inactive axon when using neurons from p75-/- mice. However, unlike the
Je et al. results, you cannot detect any proBDNF released, and when you use an antibody that blocks binding of proBDNF to p75, there is
no effect (the active synapse remains and the inactive one withdraws). Provide a possible explanation for these findings.
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