Establishing the Role of a Novel Conserved Gene in Dendrite Morphogenesis

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DESCRIPTION (provided by applicant): Many neurons receive information through elaborate dendritic arbors. The formation of dendritic arbors is under genetic control and the form of dendritic arbors correlates with function. Importantly, some forms of mental retardation have been linked to defects in dendrite development. Work in both Drosophila and vertebrates has shown that dendrite arborization is under control of dedicated transcriptional networks, the extracellular matrix and genes involved in the regulation of Golgi dynamics. The PVD sensory neurons in C. elegans were recently established as a powerful genetic system to study dendrite branching during development. In an unbiased forward genetic screen we have identified a novel, previously unstudied gene that is conserved from worms to mammals and acts in the tissues surrounding the dendrites. In this application we are using an approach that integrates both C. elegans genetics and biochemical experiments to explore for the first time the function of this gene in dendrite development. Specifically, we will determine whether the function of this gene is also required for development of other branched and unbranched neurites in C. elegans. Additionally, we will identify the vertebrate homologs of this gene. In a second series of experiments, we will determine the genetic and biochemical relationship between the newly identified gene and a transmembrane receptor that we have identified as a putative receptor that acts in neurons. Understanding such fundamental processes as dendrite development is a prerequisite for the eventual development of therapeutic and diagnostic approaches for conditions in which dendrites develop incorrectly.