Genetic analysis of nematode cell differentiation

项目摘要 我们将继续研究神经元分化所需的基因和 线虫六个触觉感受器神经元的功能 优雅女装。我们之前的研究确定了世代所需的基因， TRN的规格、维护和功能。在过去的几年里，我们 确定了指定神经元亚型所需的基因；2)发现了一种新的 转录因子的活性，包括HOX蛋白(作为“担保人”)，维持 通过限制转录因子的随机表达；3)检测 表观遗传抑制的释放如何影响细胞的终末分化 运动神经元的亚型；4)发现了几种调节TRN触摸的行为 敏感性，包括先前未研究的类型--长期敏化--以及 这些调节的潜在机制；5)确定了整合素和其他 神经元力感觉中的粘着斑蛋白；6)发现-微管蛋白 乙酰基转移酶MEC-17规定了TRN不寻常的15-原丝结构 微管；7)发现了一种新型的机械感觉伴侣 8)测定了细胞的化学计量比(MEC-42MEC-10)。 以及9)研究了Wnt信号通路Rac的作用 GTP酶和GEF在过程中产生结果。这项研究的总体目标是 未来是利用这些发现来理解单个细胞的分化是如何 类型受到控制，以及机械输入如何被感知和修改。我们计划 发现和鉴定TRN分化所需的基因，特别是那些 TRN和TRN过程的差异所需的生长和包膜 并通过调查新发现的致命性疾病来调查触摸敏感性及其控制 通过检测和鉴定TRN表达的基因来确定触觉敏感所需的基因 通过研究神经肽的作用。与健康相关的 我们的工作来自于新基因的发现和基因之间的新相互作用 这在人类和其他哺乳动物中是相似的。

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.