Mesenchymal-epithelial interactions have been shown to play a key role in controlling organogenesis. This is especially true during organogenesis of the prostate. It has been demonstrated that mesenchyme from the fetal urogenital sinus controls the morphogenesis, growth, and differentiation of prostate epithelium. Despite intensive research efforts, the molecular signals emanating from the mesenchyme important for prostate development remain largely unknown. It is our hypothesis that prostate mesenchymal-specific molecular signals are fundamental to the regulation of prostate epithelial cell proliferation and differentiation, and that such pathways are also central to the prostate cancer initiation and progression. COUP-TFs are transcription factors that belong to the nuclear receptor superfamily. Members of this transcription factor family play important roles in controlling diverse aspects of growth, development, differentiation and homeostasis throughout the animal kingdom. COUP- TFII is expressed in the mesenchymal cells of the developing prostate gland. The timing and expression pattern of COUP-TFII in the tissue are consistent with the hypothesis that it is involved in the regulation of signals, secreted by the mesenchyme, that determine epithelial cell differentiation. In order to understand to understand the precise role COUP-TFII plays a prostate organogenesis, three specific aims are proposed. A. To Study the role of COUP-TFII in prostate development using tissue-specific knockout in prostate glands. B. Determine the effect of Coup-TFII over- or under-expression on the ability of mesenchyme to induce epithelial differentiation in kidney capsule reconstitution assay. C. Identification and isolation of COUP-TF target genes in mesenchymal cells of the prostate.
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