Genetic and Molecular Analysis of Cell-Signalling in C. elegans

本研究旨在了解发育过程中诱导细胞信号传导的分子基础，以及细胞信号传导过程如何引发特定的细胞反应。特别是，该建议调查负责促进秀丽隐杆线虫生殖系有丝分裂的机制。目前，已知体细胞远端尖端细胞（somatic distal tip cell， DTC）信号传导远端生殖系，促进有丝分裂和/或阻止减数分裂。已知信号通路的三个组成部分：LAG-2，一种由DTC产生的配体；种系跨膜受体GLP-1；LAG-1，种系转录因子。这种进化上保守的信号通路在后生动物的发育和生长控制中起着普遍的作用。关于GLP-1介导的细胞间信号传导的性质，仍有许多问题有待解答。需要确定其他途径成分作为途径活动的目标。为了解决这些问题，已经确定并研究了与glp-1基因相互作用的基因。Sog突变抑制glp-1突变表型成分（如lag-1）和/或彼此（如ego-1和ego-6），而ego突变增强glp-1突变表型成分（如lag-1）。本研究的重点是在种系中促进GLP-1介导的信号传导的三个基因：ego-1、ego-3和ego-6。每个基因都有一个多效性突变表型，与多个发育方面的活动相一致。这些基因产物也可能在GLP-1介导的胚胎信号传导中起作用。拟议的实验将研究每个基因在发育中的具体作用。遗传学研究将确定在发育过程中对每个基因的需求，表型的各个方面是否相互依赖，以及每个基因产物何时活跃。为了更广泛地了解信号转导中的自我基因活动，将进行与其他已知或可疑的信号通路成分的遗传相互作用的测试。分子研究将确定每个自我基因产物的性质，并确定基因产物在发育过程中活动的时间和地点。时间允许的话，将研究基因相互作用的产物（例如，ego-1和ego-6）之间可能的物理相互作用。

Maine 9723454 This proposal aims to understand the molecular basis of inductive cell-signalling during developmental and how the cell-signalling process elicits a specific cellular response. In particular, the proposal investigates the mechanism responsible for promoting mitosis in the C.elegans germ line. Currently, it is understood that the somatic distal tip cell (DTC) signals the distal germ line, promoting mitosis and/or preventing meiosis. Three components of the signalling pathway are known: LAG-2, a ligand produced by the DTC; GLP-1, a germline transmembrane receptor; LAG-1, a germline transcription factor. This evolutionarily conserved signalling pathway plays a general role in development and growth control of metazoans. Many questions remain to be answered about the nature of intercellular signalling mediated by GLP-1. Additional pathway components need to be identified as do targets of pathway activity. To address these questions, genes that interact genetically with glp-1 have been identified and studied. Sog mutations suppress and ego mutations enhance the glp-1 mutant phenotype components (e.g., lag-1) and/or with each other (e.g., ego-1 and ego-6). This proposal focuses on three genes that promote GLP-1 mediated signalling in the germ line, ego-1, ego-3, and ego-6. Each gene has a pleiotropic mutant phenotype consistent with activity in more than one aspect of development. These gene products also may function in GLP-1 mediated signalling in the embryo. The proposed experiments will investigate the specific role of each gene in development. Genetic studies will determine the requirement for each gene during development, whether aspects of the phenotype are interdependent, and when each gene product is active. To obtain a broader understanding of ego gene activity in signal transduction, tests for genetic interactions with other known or suspected signalling pathway components will be performed. Molecular studies will determine the nature of each ego gene produ ct and confirm the time and place of gene product activity during development. Time permitting, possible physical interactions between the products of genetically interacting genes (e.g., ego-1 and ego-6) will be investigated.