The aim of the research in this proposal is to increase the understanding of general cellular and molecular mechanisms underlying morphogenesis. Towards this goal, the attachment of the uterus and vulva in the Caenorhabditis elegans model system will be examined. Formation of the C. elegans uterine-vulval connection requires the breakdown of basement membranes, the process of cellular invasion, and the establishment of de novo adhesions between cells. Similar morphogenetic processes are found during mammalian organogenesis, wound repair, angiogensis and in pathogenic conditions such as metastatic cancer. Therefore, knowledge gained from this study will likely reveal general cellular and molecular mechanisms that have important relevance to human disease and development. A pilot screen has identified the gene cog-1 (connection of gonad defect), which is critical for uterine-vulval attachment. The cog-1 gene encodes a homeodomain transcription factor that likely regulates other genes necessary for uterine-vulval attachment. The proposed research will use genetic mosaic and inducible expression experiments to determine when and in what cells COG-1 functions to regulate uterine-vulval connection. Insights from these studies will then guide a genetic screen that will identify genes regulated by COG-1 that mediate uterine-vulval attachment.