- 2007. University of Toronto. PhD.
- We have identified 35 TF genes that are expressed in subsets of medulla progenitors and neurons. By mapping these TFs onto the medulla neuroepithelium, we found that neuronal specification in the medulla is the product of the intersection of two spatial axes: (1) The temporal switch of NBs (see above); (2) in the dorsal-ventral axis, the medulla crescent–shaped neuroepithelium is sub-divided into spatial subdomains by Vsx1 (central domain), Hh (ventral), Optix (lateral) or Dpp or Wg (in two distinct regions at the tips of the crescent). While the sequential progression of neuroblasts is identical in each region, the types of neurons that are generated by a given NB are region-specific. We have determined how these two axes intersect to generate diversity in the progeny of NBs. For instance, Hth NBs generate ~800 columnar Mi1 neurons throughout the larval crescent while non-columnar Pm3 neurons, which are much fewer, are only produced by Hth NBs in the center Vsx1 region. In these central NBs, co-expression of Vsx1 and Hth leads to the neuronal expression of Seven-up and Prospero to direct the formation of ~70 non-columnar Pm3 neurons. Thus, Pm3 specification is the product of combinatorial input from both the NB (Hth) and dorsal-ventral (Vsx1) axes. We have extended this analysis to the other NBs and have mapped 7 additional neuronal-types to distinct regions in the larval neuroepithelium. We are now investigating the lineage of medulla cells and their pattern of migration in order to define how retinotopy is established: we find that columnar neurons (e.g. Mi1) are born locally throughout the larval crescent whereas non-columnar neurons (e.g. Pm3) are generated by specialized regional NBs and then migrate to take up their final position in the adult medulla cortex.
3rd instar larval optic lobe; the neural cortex of
the medulla is labeled by cut expression in green,
dvsx1 expression is labeled in red and svp in blue
- Canadian Institutes for Health Research Post-doctoral Fellowship