Genetic analysis of nematode cell differentiation

线虫细胞分化的遗传分析

• 批准号: 9276442
• 负责人: MARTIN CHALFIE
• 金额: $ 19.59万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-14 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9276442
• 关键词: Acetyltransferase; Address; Affect; Behavior; Biological Process; Caenorhabditis elegans; Cell Differentiation process; Cells; Cellular Mechanotransduction; Development; Disease; Epigenetic Process; Focal Adhesions; Generations; Genes; Goals; Guanosine Triphosphate Phosphohydrolases; HOX protein; Health; Human; Individual; Integrins; Knowledge; Lethal Genes; Maintenance; Mammals; Mechanics; Microtubules; Molecular Chaperones; Motor Neurons; Nematoda; Neuronal Differentiation; Neurons; Neuropeptides; Process; Proteins; Public Health; Research; Role; Specific qualifier value; Structure; Testing; Touch sensation; Translating; Translational Research; Tubulin; WNT Signaling Pathway; Work; cell type; genetic analysis; genetic approach; insight; novel; receptor; stoichiometry; transcription factor

Project Summary We will continue our study of genes needed for neuronal differentiation and function using the six touch receptor neurons (TRNs) of the nematode Caenorhabditis elegans. Our previous research identified genes needed for the generation, specification, maintenance and function of the TRNs. In the last few years we 1) identified genes needed for the specification of neuronal subtypes; 2) discovered a new activity of transcription factors, including Hox proteins (as “guarantors”) that maintains transcription factor expression by the restricting its stochastic expression; 3) examined the how the release of epigenetic inhibition affects the terminal differentiation of subtypes of motor neurons; 4) discovered several behaviors that modulate TRN touch sensitivity, including a previous unstudied type – long-term sensitization – and the mechanisms underlying these modulations; 5) identified a role for integrins and other focal adhesion proteins in neuronal mechanosensation; 6) discovered that the -tubulin acetyltransferase MEC-17 specifies the unusual, 15-protofilament structure of TRN microtubules; 7) discovered a new type of chaperone for the mechanosensory transduction channel; 8) determined the stoichiometry (MEC-42MEC-10) of the transduction channel; and 9) investigated the roles of the Wnt signaling pathway, Rac GTPases, and GEFs in process outgrowth. The general goal of the research going forward is to exploit these findings to understand how the differentiation of individual cell types is controlled and how mechanical inputs are sensed and modified. We plan to discover and characterize genes needed for TRN differentiation, specifically those needed for the differences among TRNs and TRN process outgrowth and ensheathment and to investigate touch sensitivity and its control by investigating newly identified lethal genes needed for touch sensitivity by testing and characterizing TRN-expressed genes for supersensitivity, and by studying the role of neuropeptides. The health relatedness of our work comes from the discovery of new genes and new interactions among genes that are similar in humans and other mammals.

项目摘要 我们将继续研究神经元分化所需的基因和 使用线虫Caenorhabdisis的六个触摸受体神经元（TRN）的功能 秀丽隐杆线。我们以前的研究确定了这一代所需的基因， TRN的规范，维护和功能。在过去的几年中，我们1） 确定的神经元亚型规范所需的基因； 2）发现了一个新的 转录因子的活性，包括维持的HOX蛋白（作为“保证”） 转录因子表达通过限制其随机表达； 3）检查 表观抑制的释放方式影响 运动神经元的亚型； 4）发现了调节TRN触摸的几种行为 灵敏度，包括以前未研究的类型 - 长期灵敏度 - 这些调制的基础机制； 5）确定整合素和其他的角色 神经元机理中的局灶性粘合剂蛋白； 6）发现微管蛋白 乙酰基转移酶MEC-17指定了TRN的不寻常的15-丝结构 微管； 7）发现了一种用于机理的新型伴侣 转导通道； 8）确定了化学计量法（MEC-42MEC-10） 转导通道； 9）研究了Wnt信号通路的作用，RAC GTPases和GEFS的过程产生。研究的一般目标 向前是探索这些发现，以了解单个细胞的差异 控制类型以及如何感测和修改机械输入。我们计划 发现并表征TRN分化所需的基因，特别是这些基因 TRN和TRN过程的差异所需的所需 并通过研究新鉴定的致命来调查触摸灵敏度及其控制 通过测试和表征TRN表达基因所需的触摸灵敏度所需的基因 用于超敏反应，并研究神经肽的作用。健康相关性 我们的工作来自发现新基因和基因之间的新相互作用 在人类和其他哺乳动物中相似。