Nuclear orphan receptor COUP-TFII in postate development

间充质-上皮相互作用已被证明在控制器官发生中起关键作用。这在前列腺的器官发生期间尤其如此。研究表明，来自胎儿尿生殖窦的间充质控制着前列腺上皮的形态发生、生长和分化。尽管进行了大量的研究工作，但对前列腺发育重要的间充质发出的分子信号在很大程度上仍然未知。我们假设前列腺间充质特异性分子信号是调节前列腺上皮细胞增殖和分化的基础，并且这些途径也是前列腺癌发生和发展的中心。COUP-TF是属于核受体超家族的转录因子。该转录因子家族的成员在控制整个动物王国的生长、发育、分化和稳态的各个方面发挥重要作用。COUP-TFII在发育中的前列腺的间充质细胞中表达。组织中COUP-TFII的时机和表达模式与其参与调节间充质分泌的决定上皮细胞分化的信号的假设一致。为了理解COUP-TFII在前列腺器官发生中的确切作用，提出了三个具体目标。A.利用前列腺组织特异性基因敲除技术研究COUP-TFII在前列腺发育中的作用。B。确定Coup-TFII过表达或低表达对间充质在肾包膜重建试验中诱导上皮分化的能力的影响。C.前列腺间充质细胞中COUP-TF靶基因的鉴定和分离。

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.