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. ***
