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

基本信息

批准号：
8583828
负责人：
Hannes Erich Buelow
金额：
$ 20.88万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
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/8583828
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

项目摘要

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（由申请人提供）：许多神经元通过精心策划的树突状乔木接收信息。树突状乔木的形成在遗传控制下，树突状arb的形式与功能相关。重要的是，某些形式的智力障碍与树突发展中的缺陷有关。果蝇和脊椎动物的工作都表明，树突植物化受到专用转录网络的控制，细胞外基质和与高尔基动力学调节有关的基因。秀丽隐杆线虫中的PVD感觉神经元最近被确立为在发育过程中研究树突分支的强大遗传系统。在公正的前遗传筛选中，我们发现了一个新颖的，以前未研究的基因，该基因从蠕虫到哺乳动物保守，并在树突周围的组织中起作用。在此应用中，我们使用的是一种整合秀丽隐杆线虫遗传学和生化实验的方法，以首次探索该基因在树突发育中的功能。具体而言，我们将确定该基因在秀丽隐杆线虫中开发其他分支和未分支神经突的功能是否也需要。此外，我们将确定该基因的脊椎动物同源物。在第二系列实验，我们将确定新鉴定的基因与跨膜受体之间的遗传和生化关系，我们已将其鉴定为作用于神经元的推定受体。理解诸如树突发展之类的基本过程是针对树突不正确发展的疾病的最终开发治疗和诊断方法的先决条件。