Exam 7: Wiring of the Nervous System

Various concentrations of Shh along the dorsoventral axis serve to activate or repress several transcription factors which then act in combination to specify neural progenitor domains and, ultimately, neurons (Figure Q7-5). The spinal cord progenitor domain in which Pax6 and Nkx6.1, but not Irx3 or Nkx2.2, are expressed will give rise to: Figure Q7-5

Motor neurons 1 and 2 start out innervating the same number of muscle fibers in a neonatal mouse. If motor neuron 1 releases more acetylcholine in the first two weeks postpartum, ultimately:

There are three Robo genes (Robo, Robo2, and Robo3) encoding receptors for Slit, which acts as a midline repellant. In homozygous Slit mutant embryos, all axons collapse at the midline, while in homozygous Robo mutant embryos, axons re-cross the midline, resulting in thinner longitudinal tracts and thicker commissures (Figure Q7-8). Figure Q7-8 What would you expect the ventral nerve cord phenotype of a triple Robo mutant (loss of function of all three Robo genes) to be? Briefly explain your reasoning.

Injecting ³H thymidine into a pregnant mouse near the end of cortical neurogenesis will label cortical excitatory neurons in layer(s):

Which of the following are sufficient for synapse formation and maturation in cultured retinal ganglion cells?

Dendritic tiling in the vertebrate retina (mutual avoidance by different neurons of the same class) is regulated by:

Roughly half of the projection neurons generated by the dorsal neuroblast are Caps⁺ and roughly half are Caps^-. Based on this information and the pattern of Caps expression in projection neurons and their glomerular targets in flies:

cAMP-signaling-deficient ORNs fail to express Nrp1 and mistarget to more anterior glomeruli. When transgenic ORNs express various versions of the β2-adrenergic receptor (Figure Q7-25), what should their relative levels of Nrp1 expression be, from lowest to highest? Figure Q7-25

Roger Sperry's chemoaffinity hypothesis presupposes that each neuron carries a unique 'ID tag' that allows it to make the appropriate connections. We estimate that the human brain is composed of about 10¹¹ neurons making 10¹⁴ synaptic connections, yet the human genome only contains about 20,000 protein-coding genes. Given that there are not enough genes to identify even a small fraction of these neurons, what strategies have evolved in order to achieve the enormous degree of wiring specificity required for normal nervous system function??

Overexpressing a single isoform of Dscam in a small subset of projection neurons shifted their dendrites to a neighboring glomerulus. Unexpectedly, the axons of their partner (wild-type) ORNs also shifted to the new glomerulus. Thus, Dscam appears to play a similar role to that of:

Motor axons expressing EphBs:

Expressing Lin44 more anteriorly also expands the localization of its receptor, Lin17 (Fz), towards the anterior. What is the expected DA9 motor neuron phenotype?

In a G_olf knockout mouse, what phenotype would you expect to see in labeled P2 axons?

In a CNG knockout mouse:

In early dorsoventral patterning studies, researchers found that transplanting a notochord from another embryo was sufficient to induce the expression of floor plate markers and motor neuron markers in a chick embryonic spinal cord explant (Figure Q7-6). What are some experiment(s) that could provide evidence that Shh is the specific signal that is both necessary and sufficient for the induction of ventral cell fates such as motor neurons? Figure Q7-6

In the ventral nerve cord of the Drosophila larva, each neuroblast (neural stem cell) divides repeatedly, regenerating itself and generating a transient ganglion mother cell with each division (Figure Q7-4). Each ganglion mother cell then divides to produce two daughter cells. At the end of this process, a full neuroblast lineage is composed of two different types of neurons, A and B, in approximately equal numbers. Figure Q7-4 A. How might these two distinct types of neurons be generated? B. What are some experiments that could be performed to test this hypothesis?

TrkB knockout mice die early in postnatal life due to an inability to feed. A. In the current model for neurotrophin and receptor function, pro-neurotrophins have high affinity for p75NTR, while mature neurotrophins act through one or more Trk receptors. Based on Figure Q7-22, would you expect a BDNF knockout mouse to have a more or less severe phenotype than the TrkB knockout? Briefly explain your reasoning. Figure Q7-22 B. Now consider the observation that many, perhaps most, neurons that express TrkB also express TrkA or TrkC. How does this alter your prediction? Assembly of Olfactory Circuits: How Do Neural Maps Form?

The clustering of acetylcholine receptors in the vertebrate neuromuscular junction requires all of the following except:

When the P2 coding region is replaced by IRES-tau-lacZ alone, the pattern of expression in the epithelium is indistinguishable from wild type, but the axons wander through the outer nerve layer, failing to converge to any particular region or glomerulus, once they enter the olfactory bulb. What can be inferred from this experiment?