Establishing the Role of a Novel Conserved Gene in Dendrite Morphogenesis

建立新型保守基因在树突形态发生中的作用

• 批准号: 8656823
• 负责人: Hannes Erich Buelow
• 金额: $ 24.8万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8656823
• 关键词: Afferent Neurons; Aging; Alleles; Animals; Axon; Behavioral; Biochemical; Biological Models; Biological Process; Caenorhabditis elegans; Cell Death; Co-Immunoprecipitations; Data; Defect; Dendrites; Development; Diagnostic; Drosophila genus; Dynein ATPase; Extracellular Matrix; Forms Controls; Foundations; Fragile X Mental Retardation Protein; Genes; Genetic; Genetic Processes; Genetic Research; Genetic Screening; Golgi Apparatus; Grant; Homologous Gene; Intervention; Invertebrates; Kinesin; Label; Lesion; Ligands; Link; Mammals; Mental Retardation; Molecular; Molecular Analysis; Morphogenesis; Mus; Nematoda; Nervous system structure; Neurites; Neurons; Organism; Pathway interactions; Phenotype; Process; Proteins; Regulation; Reporter; Role; Series; Skin; Structure; Study models; System; Testing; Therapeutic Intervention; Time; Tissues; Transgenic Animals; Transgenic Organisms; Vertebrates; Work; axon guidance; base; behavior test; fly; gain of function; gene function; genetic analysis; human disease; intellectual and developmental disability; loss of function; man; mutant; neural circuit; novel; public health relevance; receptor; research study; therapeutic development

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.

描述（申请人提供）：许多神经元通过复杂的树突状乔木接收信息。树突状乔木的形成受遗传控制，树突状乔木的形式与功能相关。重要的是，某些形式的智力迟钝与树突发育缺陷有关。在果蝇和脊椎动物中的工作表明，树突树枝化是在专用的转录网络，细胞外基质和基因参与调节高尔基体动力学的控制下。C.秀丽隐杆线虫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。在一个公正的向前遗传筛选，我们已经确定了一个新的，以前未研究的基因，是保守的蠕虫哺乳动物和行为的树突周围的组织。在这个应用程序中，我们使用的方法集成了C。elegans遗传学和生化实验，首次探索该基因在树突发育中的功能。具体来说，我们将确定该基因的功能是否也是C中其他分支和无分支神经突发育所需的。优美的此外，我们将确定该基因的脊椎动物同源物。在第二系列的 通过实验，我们将确定新发现的基因和跨膜受体之间的遗传和生物化学关系，我们已经确定跨膜受体是一种假定的神经元受体。了解树突发育等基本过程是最终开发树突发育不正确的治疗和诊断方法的先决条件。