Development and Microcircuitry Dissection of the Retina

The visual system in both vertebrates and invertebrates require a precise topographic map, with the correct neuronal subtype specified in a tightly regulated spatiotemporal fashion. We are interested in using the fly optic lobe to model the vertebrate retina.

Our first aim is to elucidate the signaling mechanisms that regulate all stages of retina development: from the proliferation of progenitor cells and initial cell fate specification to proper synapse targeting and layer formation. We and others have identified Jak-Stat, Notch, EGFR, and Hippo pathways to be important for regulating the molecular switch from symmetric to asymmetrically dividing cells. We are trying to further understand how extracellular signals can ultimately affect cell fate decisions in the medulla.

Secondly, we hypothesize that like the vertebrate model,the time of birth can specify a given retinal cell type. Recent work by the Sato group has shown that four transcription factors specify the birth of medulla neurons (Hth, Drf, Run, and Bsh). To test our hypothesis on the temporal requirement of neuronal birth order, we will birthdate different retinal subtypes that make up a single module in the optic lobe, the so-called 'column' by making single-cell FRT clones by MARCM. If both of these hypotheses turn out to be correct, that is, if cell fate is ultimately controlled by local cell-to-cell interactions (from first aim), this will represent a highly useful fly model which resembles the vertebrate nervous system much more than the strictly intrinsically specified lineages that make up the central brain.

Group Member: Kathy Ngo