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

缅因州9723454 该建议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激发特定的细胞反应。 特别是，该提案调查了负责促进秀丽隐杆线虫生殖系有丝分裂的机制。 目前，可以理解的是，体细胞远端细胞（DTC）向远端生殖系发出信号，促进有丝分裂和/或阻止减数分裂。 已知信号通路的三个组分：LAG-2，由DTC产生的配体; GLP-1，生殖系跨膜受体; LAG-1，生殖系转录因子。 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，仍有许多问题有待回答。 其他途径的组成部分，需要确定的途径活动的目标。 为了解决这些问题，与glp-1基因相互作用的基因已经被鉴定和研究。 Sog突变抑制和ego突变增强glp-1突变体表型成分（例如，LAG-1）和/或彼此（例如，ego-1和ego-6）。 该提案集中在生殖系中促进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体表型，与发育的一个以上方面的活性一致。 这些基因产物也可能在胚胎中GLP-1介导的信号传导中起作用。 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。 为了更广泛地了解自我基因在信号转导中的活性，将进行与其他已知或疑似信号通路组分的遗传相互作用测试。 分子研究将确定每个自我基因产物的性质，并确认基因产物在发育过程中活动的时间和地点。 如果时间允许，遗传相互作用基因的产物之间可能的物理相互作用（例如，ego-1和ego-6）将被调查。

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.