Genetic and Molecular Analysis of Oocyte Meiotic Prophase Arrest in C. elegans

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9506220 Schedl Arrest of the cell cycle in prophase of meiosis I is a conserved feature of oogenesis in essentially all multicellular animals. Oocytes in organisms from starfish to humans maintain this arrested state until ovulation by a mechanisms that is not well understood. This proposal introduces a genetic strategy for isolating and characterizing molecular regulators of meiotic prophase cell cycle arrest. Recent genetic screens performed in the nematode Caenorhabditis elegans have identified mutants where oocyte arrest in diakinesis of MI prophase fails to be maintained. In oar-1 and oar-2 mutants (oar= oocyte meiotic prophase arrest defective), oocytes leave arrest and endomitotically replicate their DNA. Strategies have been developed to distinguish Oar mutants from other mutants producing endomitotic oocytes. Importantly, a mutant has been obtained with a phenotype opposite to Oar; olk-1 (olk= oocyte arrest lock) oocytes maintain arrest under conditions when arrest is usually lost. It is likely that the pathway for maintenance of meiotic arrest defined by the oar and olk genes involves cell cell communication from the soma to the oocyte. Analysis of oar-1 is consistent with the conclusion that a cell cell signal is needed to maintain meiotic arrest; cloning reveals that oal-1 encodes a Sec61p gamma protein known in other systems to facilitate protein translocation into the ER, and mosaic analysis shows oar-1 activity is needed specifically in the germline to prevent loss of oocyte arrest. Oar-1 may therefore act to translocate a transmembrane receptor to the oocyte surface for reception of the arrest signal. This proposal will initiate a more extensive genetic and molecular investigation of the pathway maintaining oocyte meiotic prophase arrest in C. elegans. Dr. Schedl will:1) Identify genes necessary for oocyte meiotic prophase arrest using a genetic screen, 2) Genetically and phenotypically characterize mutants in the oar collection, and 3) Genet ically characterize the arrest "loc-1" mutant, olk-1. ***