Molecular Mechanisms of Differentitation and Tissue Specific Gene Regulation

Based on their critical roles in sexual differantiation and reproductive function, electrolyte balance and intermediary metabolism, considerable attention has been directed at defining the machanisms that control the biosynthesis of steroid hormones. A m ajor result of such studies was the cloning of the transcription factor Steroidogenic Factor (SF-1). This factor stimulates steroidogenesis through the activation of genes that encode proteins required for the steroidogenic pathway. Often, the same tran scription factors that are used to activate genes for that cell-type's specific products are also used during the differentation of a particular cell type. This appears to hold through for SF-1 as well, since SF-1 is expressed at the earliest development al stages of the urogenital ridge and because SF-1 knockout mice fail to develop steroidogenic tissues. A major goal of our studies is to define the transcriptional mechanisms that guide cell- and stage-specific onset of SF-1. We hy pothesize that such results will helpt to unravel the molecular pathways behind commitment to the steroidogenic cell-lineage. In addition, we are interested in defining how SF-1 integrates cell signaling and gene transcription in differentiated cells. S pecifically, we are investigating how the transactivation capacity of SF-1 is affected through posttranslational modifications and interactions with other proteins.