SERTOLI CELL DIFFERENTIATION AND TESTIS DEVELOPMENT

拟议的研究旨在更好地了解 控制和维持睾丸发育的机制，在 特别是特定类别的转录因子 规范这一过程。重点是阐明 支持细胞分化的转录调控。支持细胞 上皮细胞是胚胎睾丸的始动细胞吗？ 成人睾丸中精子发生的发育和维持。 初步研究表明，一类独特的 转录因子，碱性螺旋-环-螺旋蛋白(BHLH)出现 参与Sertoli细胞分化，因此对 睾丸发育。被检验的假设是支持细胞基本 螺旋-环-螺旋蛋白在转录过程中是必不可少的 Sertoli细胞分化的调节及其对正常的关键 睾丸的发育和功能。更具体地说，荷尔蒙和 局部产生的旁分泌因子促进支持细胞分化 通过特定的bHLH蛋白在不同阶段的表达 睾丸发育异常和男性不育可能 部分原因是支持细胞转录调控不当 涉及这些bBLH蛋白的分化。实验性的 该方法包括以下具体目标。1)调查 BHLH蛋白在支持细胞分化中的作用2)调查 Sertoli基因表达的发育调控。3) 探讨Sertoli bHLH蛋白在不同发育阶段的生理功能 睾丸发育。这些研究的完成将提供 洞察Sertoli细胞的转录调控 睾丸发育过程中的分化。支持细胞分化 对胚胎、青春期前、青春期和成人的睾丸来说是必不可少的 发展。支持细胞分化异常可导致 不孕不育和一些出生缺陷。不恰当地表达 支持细胞基因如SRY和MIS会导致性别等缺陷 反转，含糊的性腺，和消失的睾丸。男性不育会 部分也是由于Sertoli的转录调控异常 细胞分化。因此，来自当前提案的意见 支持细胞分化意愿的转录调控 更好地了解正常和异常的睾丸发育 和功能。

The proposed research is designed to develop a better understanding of the mechanisms that control and maintain testis development, in particular the manner by which a specific class of transcription factors regulate this process. Emphasis is placed on the elucidation of the transcriptional control of Sertoli cell differentiation. Sertoli cells are the epithelial cells responsible for the onset of embryonic testis development and the maintenance of spermatogenesis in the adult testis. Preliminary research has demonstrated that a unique class of transcription factors, basic helix-loop-helix proteins (bHLH), appear to be involved in Sertoli cell differentiation and thus important for testis development. The hypothesis tested is that Sertoli cell basic helix-loop-helix proteins are essential in the transcriptional regulation of Sertoli cell differentiation and critical for normal testis development and function. More specifically that hormones and locally produced paracrine factors promote Sertoli cell differentiation through the expression of specific bHLH proteins at various stages of testis development Abnormal testis development and male infertility may in part be due to inappropriate transcriptional control of Sertoli cell differentiation involving these bBLH proteins. The experimental approach consists of the following specific aims. 1) Investigate the role of bHLH proteins in Sertoli cell differentiation. 2) Investigate the developmental regulation of Sertoli bHLH gene expression. 3) Investigate the physiological function of Sertoli bHLH proteins during testis development. The completion of these studies will provide insight into the transcriptional regulation of Sertoli cell differentiation during testis development. Sertoli cell differentiation is essential for embryonic, prepubertal, pubertal and adult testis development. Abnormal Sertoli cell differentiation can cause infertility and a number of birth defects. Inappropriate expression of Sertoli cell genes such as SRY and MIS results in defects such as sex reversal, ambiguous gonads, and vanishing testis. Male infertility will also in part be due to abnormal transcriptional regulation of Sertoli cell differentiation. Therefore, observations from the current proposal on transcriptional regulation of Sertoli cell differentiation will provide a better understanding of normal and abnormal testis development and function.