2015. Rockefeller University. PhD.
How neuronal circuits in the brain are assembled is a crucial question in developmental neurobiology. The highly ordered visual centers and tractable genetics in Drosophila allow for an elegant model to study this problem. The medulla is the most complex neuropil in the Drosophila optic lobe, and comprises 80-100 different cell types. Medulla neurons are produced by the Outer Proliferation Center (OPC), a crescent-shaped neuroepithelium within the developing optic lobe. Our lab has identified three processes that generate the diversity of the over 80 medulla cell types. First, each of the ~800 neuroblasts (NBs) sequentially expresses a series of six temporal transcription factors (tTFs) whose combination specifies different types of neuronal progeny. The integrated output of this system allows each NB to specify about 20 types of uni-columnar (UC) neurons in the medulla, i.e. 800 neurons of each type existing at a 1:1 ratio to the number of ommatidia. Second, Notch signaling (on or off) diversifies identity of the two neurons emerging from the division of the ganglion mother cell, the single transit-amplifying descendant of each NB. Finally, spatial cues within the OPC neuroepithelium act in combination with tTFs to specify the fate of a second set of neurons—multi-columnar (MC) neurons—that have a larger receptive field, innervate anywhere from two columns to half of the medulla, and exhibit less than a 1:1 ratio of neurons to columns. While MC neurons derive from restricted regions of the OPC (e.g. the Vsx domain of the OPC in the case of Pm3a/b neurons), most MC neuronal types consistently target the entire medulla. The mechanisms behind how such neurons find their targets are mostly unknown. My work seeks to understand how MC neurons are specified, and how this fate specification informs the cell’s decisions in axon guidance, and thus, the establishment of retinotopy in this system. Understanding how complex neurons are generated and find multiple targets on the retinotopic map will enable us to better comprehend basic principles of nervous system assembly.
NIH NRSA Individual Postdoctoral Fellowship (F32)