Establishing the Role of a Novel Conserved Gene in Dendrite Morphogenesis

描述(申请人提供)：许多神经元通过精细的树突状乔木接收信息。树枝的形成受遗传控制，树枝的形态与功能有关。重要的是，某些形式的智力低下与树突发育缺陷有关。在果蝇和脊椎动物中的研究表明，树突的树枝形成受到专门的转录网络、细胞外基质和参与高尔基体动力学调节的基因的控制。线虫的PVD感觉神经元是最近建立的一个强大的遗传系统，用于研究发育过程中的树突分支。在一个无偏见的正向遗传筛查中，我们发现了一种新的、以前未被研究过的基因，它从蠕虫到哺乳动物都是保守的，并在树突周围的组织中发挥作用。在这项应用中，我们使用了一种结合线虫遗传学和生化实验的方法，首次探索了该基因在树突发育中的功能。具体地说，我们将确定该基因的功能是否也是线虫其他分枝和不分枝神经突起发育所必需的。此外，我们还将鉴定该基因的脊椎动物同源物。在第二个系列中 在实验中，我们将确定新发现的基因和跨膜受体之间的遗传和生化关系，我们已经确定了跨膜受体是一种可能作用于神经元的受体。了解树突发育这样的基本过程是最终开发治疗和诊断树突发育不正确的条件的方法的先决条件。

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.