CONTROL OF EARLY DEVELOPMENT IN C ELEGANS

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How the one-cell embryo generates the diverse array of tissues seen in adult organisms remains one of the central unsolved problems in development. In the nematode C. elegans, as in many species, this process is guided mainly by maternally supplied factors. My lab is taking advantage of the powerful genetics available in C. elegans to identify some of the genes that control this process. We have screened for mutations in genes that encode maternal components required for the specification and development of a specific cell type, the germ line. We have focussed on the germ line because it is not required for viability and mutant animals lacking germ cells are easily identified. We have isolated mutations that result in maternal-effect sterility or a "grandchildless" phenotype: homozygous mutant hermaphrodites produced by heterozygous mothers are themselves fertile but produce sterile progeny. Our screens have identified surprisingly few genes: six mes (for maternal- effect sterile) loci, defined by 23 mutations. The five characterized loci appear to belong to two classes. Embryos produced by mes-1 mutant mothers display defects in cytoplasmic partitioning during the division that generates the germ-line founder cell. The resulting larvae lack germ-line progenitor cells and contain extra body muscle cells. In contrast, the progeny of mes-2, mes-3, mes-4, and mes-6 mothers undergo normal embryogenesis, but show severe defects in post-embryonic proliferation of the germ line, resulting in agametic adults with 100-1000-fold reductions in germ cells. Our proposed experiments will address the following questions: Do mutations in mes-1 cause the germ-line founder cell to follow the fate of its sister, a muscle progenitor? Is this the null phenotype, or do more severe alleles affect earlier partitioning events and lead to embryonic lethality? Do the proliferation defects caused by mutations in mes-2, mes-3, mes-4, and mes-6 reflect defective determination of the germ line or an inability of the germ cells to execute their lineage? Are these mes gene products required in the germ line or in the somatic gonad? In addition to phenotype analysis, we will clone and molecularly analyze mes-1, mes-3, mes-4, and mes-6. Through immunolocalization of their gene products, we will learn whether any are partitioned to the germ line during early embryogenesis and whether any are germ-granule components. Finally, we will screen for and characterize mutations in additional mes loci. Our studies will elucidate the nature, localization, and function of maternal factors that participate in generating a functional germ line.