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 determine the shape of dendritic arbors. In mammals, some dendritic filopodia have been shown to be precursors to 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 analyze and identify either new genes or genes not previously known to regulate neuronal dendrites. From this proposal we hope to identify signaling molecules and pathways that regulate neuronal dendrite development. As 72% of all human neurological disease genes can be found in Drosophila, orthologues of such genes identified herein may be candidates to play a role in mammalian dendrite development and potentially human neurodevelomental disorders as well.
