gld-I , a Tumor Suppressor Gene Required for Oocyte Development in Caenorhabditis elegans

We have characterized 31 mutations in the gld-1 (defective in germline development) gene of Caenorhabditis elegans. In gld-1 (nul l ) hermaphrodites, oogenesis is abolished and a germline tumor forms where oocyte development would normally occur. By contrast, gld-1 (null) males are unaffected. The hermaphrodite germline tumor appears to derive from germ cells that enter the meiotic pathway normally but then exit pachytene and return to the mitotic cycle. Certain gld-1 partial loss-of-function mutations also abolish oogenesis, but germ cells arrest in pachytene rather than returning to mitosis. Our results indicate that gld-l is a tumor suppressor gene required for ocyte development. The tumorous phenotype suggests that gld-I( + ) may function to negatively regulate proliferation during meiotic prophase and/or act to direct progression through meiotic prophase. We also show that gld-I( +) has an additional nonessential role in germline sex determination: promotion of hermaphrodite spermatogenesis. This function of gld-1 is inferred from a haplo-insufficient phenotype and from the properties of gain-of-function gld-1 mutations that cause alterations in the sexual identity of germ cells. G ERMLINE development in multicellular organisms represents a specialized example of cell determination and differentiation. In most metazoans, primordial germ cells are set aside early in development and subsequently expanded by proliferation. At later stages, germ cells enter the meiotic pathway and begin gametogenesis. At a minimum, germline development thus requires mechanisms to ( 1 ) control germ cell proliferation and entry into the meiotic pathway, ( 2 ) specify sexual identities and ( 3 ) direct the differentiation of germ cells as either sperm or oocytes. Studies of germline development in Caenwhabditis ekguns have begun to provide detailed models for the processes that control germ cell sexual identity and entry into the meiotic pathway. Sexual fates in the nematode soma and germline are governed by similar regulatory hierarchies that are set in response to the X chromosome to autosome ratio ( XA ratio) ( MADL and HERMAN 1979; reviewed by VILLENEUVE and MEYER 1990). Animals with a single Xchromosome ( XA ratio = 0.5) develop as males, whereas animals with two X chromosomes (XA ratio = 1) develop as self-fertile