For a nervous system to be wired correctly, the axons have to be guided toward the correct targets and the dendrites need to have the correct branching patterns. At present, much less is known about the molecular mechanisms that control dendrite branching as compared to that control axon guidance. The goal of this application is to use Drosophila genetics to identify """"""""Core programs"""""""" that control dendrite development. For this purpose, recently, we developed a simple assay system. By using fly transgenic technique, we express Green Fluorescence Protein (GFP) in the multiple dendritic (MD) neurons, a group of sensory neurons with stereotyped dendritic branching pattern. This method allows us to visualize the development of the dendrites of MD neurons in the living fly embryos and thereby provides an excellent assay system for a genetic dissection of dendrite development. In a pilot screen, we were able to use this assay system to identify and characterize dendrite mutants. We propose to do a systematic and near saturation screen to identify the great majority of the genes that are required to control the dendrite development in Drosophila. We will carry out in depth phenotypic and molecular studies of the """"""""Key genes"""""""" identified from this mutant screen. These key genes should lead to the identification of """"""""Core programs"""""""" that control dendrite development. Given the striking conservation of many molecular mechanisms that control various developmental processes including axon guidance, it is highly likely that the molecular mechanisms controlling dendrite development is conserved between fly and mammals. The Core programs identified from this work should help unravel the molecular control of dendrite development in mammals and contribute to the understanding and eventual treatment of neurological diseases in Human.
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