Genetic Analysis of Dendrite and Dendritic Filopodia Formation

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DESCRIPTION (provided by applicant): In the brain, most information processing physically occurs on neuronal dendrites. Understanding how dendrites and dendritic structure develop and function is critical to understanding normal cognition and what may be perturbed in human cognitive disorders and retardation syndromes. Evidence for altered dendritic morphology exists in Alzheimers, Fragile X, and Downs syndrome. In some vertebrates there is evidence that dendritic filopodia help form dendritic arbors. In mammals, at least some dendritic filopodia can become dendritic spines. In Drosophila, we are able to visualize dendrites and dendritic filopodia in optically transparent intact animals. We believe the study of dendrites and dendritic filopodia development using a simple but powerful genetic model, should yield insights into more complex mammalian dendrite development. Our approach combines a genetically amenable organism, Drosophila, with high-resolution microscopy to perform large-scale forward genetics to identify genes and signaling pathways regulating dendritic development. We are also investigating the roles of CaMKII, a molecule implicated in learning and memory, as a potent regulator of dendritic structure in Drosophila. As 72% of all human neurological disease genes are found in Drosophila, orthologues of such genes identified herein may be candidates to play a role in mammalian dendrite development and potentially human disease.