The long-term goal of the Hanna-Rose laboratory is to elucidate the molecular mechanisms that direct organogenesis. The focus of the proposed research is a detailed investigation of the role of the cog-2 gene and of a specific cell-cell fusion in promoting proper attachment of the C. elegans uterus and vulva. cog?2 encodes a Sox (SRY-related HMG box) family transcription factor that is expressed in a specific cell of the uterus called the uterine seam cell (utse). The utse normally executes a developmentally programmed cell fusion to another gonadal cell called the anchor cell. This cell-cell fusion promotes formation of an open channel between the uterus and the vulva in a late stage of organogenesis. In the absence of cog-2 function, utse cell fate is induced but fusion to the anchor cell (AC) is not executed. The aims of the proposed research are to determine whether COG-2 acts to regulate fusion directly or affects fusion indirectly through an effect on utse cell fate, to identify and characterize additional genes involved in AC-utse fusion, and to identify COG-2 binding partners. Results are expected to elucidate mechanisms whereby COG-2 functions. This will also shed light on potential regulatory targets for vertebrate Sox proteins. Furthermore, the results are expected to increase our understanding of how the formation of a proper connection between two organs is genetically programmed and to promote the development of tools for probing the mechanism of cell fusion.