Genetic and Molecular Analysis of Cell-Signaling in Development in Caenorhabditis Elegans

本研究的长期目标是阐明多细胞生物发育过程中调控细胞信号的分子基础。本研究特别研究了秀丽隐杆线虫中两种调控相互作用的机制：在种系中诱导有丝分裂和在早期胚胎中诱导前咽。尽管这两种细胞信号过程发生在不同的组织和不同的发育时期，但它们至少有一个共同的成分：glp-1基因。广泛的遗传、分子和免疫细胞化学研究表明，glp-1在这些诱导组织中作为信号受体。由glp-1相关受体介导的细胞信号通路在后生动物的发育和生长控制中发挥着普遍作用：果蝇和秀丽隐杆线虫的同源物介导发育过程中的调节细胞信号传导，脊椎动物的同源物是原癌基因。关于glp-1及其相关受体介导的细胞间信号通路的了解相对较少。作为鉴定glp-1介导途径的其他组分的一种手段，产生了glp-1突变的外基因抑制因子和增强因子。glp-1的抑制因子和增强因子可能是由glp-1介导的细胞间信号通路中其他基因的突变。本研究的重点是两个隐性抑制基因，sog-1和sog-10，以及一组隐性增强基因（自我）突变。提出了分析这些抑制和增强基因在种系和胚胎细胞-细胞相互作用中的作用的遗传和分子研究。1) sog-1基因已被充分表征；它可能是一个冗余基因家族的成员。本文概述了sog-1产物及其在发育过程中的表达和定位模式的分子分析。2)初步完成sog-10的遗传和表型分析；在这里，提出了一个更详细的遗传分析，将描述sog-10在发育中的一般作用。随后的分子分析将描述基因产物及其在发育过程中的表达和定位模式。3)对一组自我突变进行有限的遗传分析，以确定哪个自我基因最有可能编码glp-1介导的细胞间信号通路的组成部分。这个特殊的自我基因将进行遗传分析，以确定其在生殖细胞增殖和其他方面的发展中的作用。＊＊＊

9318709 Maine The long range goal of this proposal is to elucidate the molecular basis of regulatory cell signaling during development of multicellular organisms. In particular this proposal investigates the mechanisms underlying two such regulatory interactions in the nematode, Caenorhabditis elegans: induction of mitosis in the germ line and induction of the anterior pharynx in the early embryo. Although these two cell signaling processes occur in different tissues and at different times in development, they share at least one common component: the glp-1 gene. Extensive genetic, molecular, and immunocytochemical studies suggest that glp-1 acts as a signal receptor in each of these induced tissues. Cell signaling pathways mediated by glp-1 related receptors play a general role in metazoan development and growth control: Drosophila and C. elegans homologs mediate regulatory cell signaling during development and vertebrate homologs are proto-oncogenes. Relatively little is known about the intercellular signaling pathways mediated by glp-1 and related receptors. As a means of identifying other components of the glp-1 mediated pathway, extragenic suppressors and enhancers of glp-1 mutation were generated. Suppressors and enhancers of glp-1 are likely to be mutations in other genes in the intercellular signaling pathway mediated by glp-1. This proposal focuses on two genes identified as recessive suppressors, sog-1 and sog-10, and on a set of recessive enhancer (ego) mutations. Genetic and molecular studies that analyze the roles of these suppressor and enhancer genes in germline and embryonic cell- cell interactions are proposed. 1) sog-1 has been well characterized genetically; it may be a member of a redundant gene family. Here, a molecular analysis is outlined that will describe the sog-1 product and its expression and localization patterns during development. 2) A preliminary genetic and phenotypic analysis of sog-10 has been completed; here, a more det ailed genetic analysis is proposed that will describe the general role of sog-10 in development. A subsequent molecular analysis will describe the gene product and its expression and localization patterns during development. 3) A limited genetic analysis of a set of ego mutations will be done to identify which ego gene is most likely to encode a component of the glp-1 mediated intercellular signaling pathway. This particular ego gene will be genetically analyzed to determine its role in germline proliferation and other aspects of development. ***