For a nervous system to be wired properly, the axons have to be guided toward the correct targets and the dendrites need to have the correct branching pattern. At present, much less is known about the molecular mechanisms that control dendrite branching as compared to those that control axon guidance. The goal of this proposal is to use Drosophila genetics to identify """"""""Core programs"""""""" that control dendrite development. For this purpose, recently, we developed and further refined a simple assay system. By using fly transgenic technique, we express Green Flourescent Protein (GFP) in specific classes of multiple dendritic (MD) neurons, a group of sensory neurons with class-specific dendritic branching pattern. This 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. We have used this assay system to identify and characterize dendrite mutants and have already made considerable progress in identifying """"""""Key genes"""""""" that control different aspects of dendrite development and have begun to gain mechanistic insights. We propose to extend this work by doing 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 identifications 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 will contribute to the understanding and eventual treatment of human neurological diseases many of which have pathology in dendrites. ? ?

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Neurodifferentiation, Plasticity, and Regeneration Study Section (NDPR)
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Riddle, Robert D
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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