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

9318709缅因州这项提议的长期目标是阐明多细胞生物体发育过程中调节细胞信号的分子基础。特别是，这项建议研究了线虫中两种这样的调控相互作用的机制：诱导胚系有丝分裂和诱导早期胚胎的前咽。虽然这两个细胞信号传递过程发生在不同的组织和发育的不同时间，但它们至少有一个共同的组成部分：GLP-1基因。广泛的遗传、分子和免疫细胞化学研究表明，GLP-1在这些诱导的组织中都扮演着信号受体的角色。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起着普遍的作用：果蝇和线虫同源物在发育过程中介导调节细胞信号，脊椎动物同源物是原癌基因。GLP-1及其相关受体介导的细胞间信号转导通路知之甚少。作为鉴定GLP-1途径的其他成分的手段，产生了GLP-1突变的基因外抑制和增强子。GLP-1的抑制子和增强子很可能是GLP-1介导的细胞间信号通路中其他基因的突变。这项建议关注两个被确认为隐性抑制基因sog-1和sog-10的基因，以及一组隐性增强子(EGO)突变。提出了分析这些抑制基因和增强基因在生殖系和胚胎细胞-细胞相互作用中的作用的遗传学和分子研究。1)SOG-1基因特征明确，可能是一个冗余基因家族的成员。在这里，概述了分子分析，将描述SOG-1的产物及其在发育过程中的表达和定位模式。2)已经完成了SOG-10的遗传和表型分析；在这里，我们提出了一个更详细的遗传分析，它将描述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EGO突变进行有限的遗传分析，以确定哪个EGO基因最有可能编码GLP-1介导的细胞间信号通路的一个组成部分。这种特殊的自我基因将被遗传分析，以确定它在生殖系增殖和其他发育方面的作用。***

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. ***