GLD-1, A TUMOR-SUPPRESSOR GENE REQUIRED FOR OOCYTE DEVELOPMENT IN CAENORHABDITIS-ELEGANS

We have characterized 31 mutations in the gld-l (defective in germline development) gene of Caenorhabditis elegans. In gld-1(null) hermaphro dites, oogenesis is abolished and a germline tumor forms where oocyte development would normally occur. By contrast, gld-1(null) males are u naffected. The hermaphrodite germline tumor appears to derive from ger m cells that enter the meiotic pathway normally but then exit pachyten e and return to the mitotic cycle. Certain gld-1 partial loss-of-funct ion mutations also abolish oogenesis, but germ cells arrest in pachyte ne rather than returning to mitosis. Our results indicate that gld-1 i s a tumor suppressor gene required for oocyte development. The tumorou s phenotype suggests that gld-1(+) may function to negatively regulate proliferation during meiotic prophase and/or act to direct progressio n through meiotic prophase. We also show that gld-1(+) has an addition al nonessential role in germline sex determination: promotion of herma phrodite spermatogenesis. This function of gld-1 is inferred from a ha plo-insufficient phenotype and from the properties of gain-of-function gld-1 mutations that cause alterations in the sexual identity of germ cells.