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Mini-Quiz 2
2/14/06
1. A single progenitor in the ventricular zone is labeled retrovirally (i.e. via insertion of a
retroviral genome) at an early stage in cortical development (when layer 6 neurons are
being made). Daughters of this progenitor are identified via the retroviral marker and the
layer(s) to which they migrate are examined well after the time when the cortical plate is
formed. It was found that the daughters are found not only in layer 6, but also in other
layers. Explain briefly why. (Hints: Recall how progenitors divide, and keep in mind the
results in the Kaznowski/McConnell paper).- 0.5
Early in development, progenitors undergo asymmetric cell division to
generate a postmitotic neuron and a neuroblast. The neuroblast that is formed
continues this process of asymmetric cell division until the end of the period of
ventricular zone neurogenesis. The neurons that are formed at different times
migrate to whatever layer is being generated at the time resulting in the marked
daughter neurons being found in multiple layers.
1b) Dab1 is a key molecule in the reelin signaling pathway. At a late stage in
neurogenesis (when upper layer neurons are being formed), you manage to generate
neurons some of which are Dab1-positive and some are Dab1-negative. You then follow
them to see where they end up migrating. Which layers might you expect the Dab1
negative population to end up in if Dab1 works: - 1
i) cell autonomously?
in deeper layers like in the Dab1 KO or reeler mouse.
ii) non cell-autonomously?
In upper layers since the Dab1-positive neurons might influence their migration.
2. What is the key experiment in the Fukuchi-Shimoguri and Grove paper that indicated
that FGF8 is instructive, and not merely permissive, for cortical patterning? – 0.5
Introduction of FGF8 at an ectopic location i.e. the posterior, resulted in the
formation of an ectopic S1 cortex.
3. What would the phenotype be (more neurons or more ectoderm) if you:
a) Expressed a constitutively nuclear localized Notch intracellular domain in a presenilin
mutant? – 0.5
More ectoderm since regardless of whether or not presenilin is present, the NICD
will result in the downregulation of proneural genes.
b) Expressed a constitutively nuclear localized Notch intracellular domain which had the
region that interacts with CSL proteins deleted? 0.5
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More neurons since this mutant Notch cannot interact with CSL proteins and thus,
cannot turn on E(Spl) type genes. So proneural genes remain on.
4. BRIEFLY mention two similarities between the mechanisms by which Drosophila
neuroblasts and cortical progenitors act to generate progeny. (Hint: Recall both lectures
and papers discussed) – 1
Several possibilities: each divides asymmetrically to produce another neuroblast
and neurons; each progressively loses competence over time; each produces multiple
types of neurons/glia; each produces progeny in defined temporal order; in each
case, postmitotic neurons can no longer respond to intrinsic (flies) or extrinsic
(cortex) cues to change their competence;
5) Define in one sentence each: - 1
i) Equivalence group
Group of cells with initially equivalent developmental potential
ii) Protocortex model of cortical plate formation
Model which suggests that cortical areas are defined by incoming thalamocortical
projections and not by intrinsic underlying patterning mechanisms.
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