One of the central questions of developmental biology is how cells generated by cleavage become committed to different developmental fates. This process, termed determination, is poorly understood despite nearly a century of research. One possible mechanism of determination is that maternally specified cytoplasmic components (determinants) are asymmetrically partioned during cleavage and direct specific developmental programs in the cells that receive them. The long term goal of the proposed research is understanding of the cellular and molecular mechanisms of determination. Understanding the basis for the initiation of developmental programs will help to understand how developmental programming can go awry leading to birth defects and cancer. Specifically, the proposed research includes 1) Analysis of the products of five par genes encoding functions required for proper cytoplasmic partitioning in early embryos of the nematode Caenorhabditis elegans, 2) Identification and analysis of genes that interact with the par genes 3) Analysis of three genes involved in determination of the intestine. Analyses will include completion of genetic and phentoypic studies of the five par genes, isolation of DNA corresponding to the genes, computer assisted analysis of the structure of the products of the genes, and analysis of the temporal and spatial distribution of the gene products in situ using antibodies directed against fusion proteins made in E. coli. Genes that interact with the par genes will by identified by mutations that suppress or enhance par mutations. In addition, we will study a new set of genes defined by mutations that appear to specifically block the differentiation, maintenance or determination of intestinal cells. These mutations affect the behavior of the cells in the E lineage, which gives rise exclusively to the intestine, and so are called eli mutations. These two groups of mutations provide a unique opportunity to investigate two aspects of determination in early embryos. The par mutations should provide insight into the mechanism of cytoplasmic localization and the eli mutations should provide information about the mechanism of determination of the intestine.
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