The specification of germ cells to develop as sperm or oocyte is a process that is fundamental to all sexually reproducing metazoans. I am focusing on two genes that control germline sex determination in Caenorhabditis elegans, fog-2 and oop-1. The goal is to understand at the genetic and molecular level how these genes specify germline sexual fate. My genetic analysis has revealed that fog-2 is regulated in a temporal, germline specific, and sex specific manner. In turn, fog-2 regulates sex determination genes downstream in the pathway in specify spermatogenesis in the hermaphrodite germline. The proposed molecular analysis of fog-2 will provide basic information about the structure and expression of the fog-2 gene and distribution of the gene product. Such information will reveal if fog-2 is regulated at the level of RNA or protein accumulation. Genetic models for how fog-2 regulates downstream sex determination genes will be tested in vivo with a fog-2 mRNA microinjection assay. I have isolated mutations that define a new locus, oop-1 which controls the diverse germline processes of sex determination, proliferation and gametogenesis. One allele has a recessive germline tumorigenic phenotype. The proposed genetic analysis of oop-1 will reveal the range of processes that it controls and allow me to determine whether the oncogenic phenotype is a consequence of loss-of-gene-function or a rare mutant activity. Proposed molecular analysis will provide information about the structure of oop-1 and its possible relationship to genes that control proliferation and development in other eukaryotes. The health relatedness of the proposed work is two-fold. First, research on development in simple, experimentally accessible, metazoan systems as C. elegans provides information about fundamental processes that are involved in development of all animals, including humans. Second, our knowledge about genes in which recessive mutations cause neoplasia is rudimentary. Analysis of oop-1 offers the possibility that it will provide clues about such """"""""recessive oncogenes"""""""" that may be applicable to human cancer.
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