Regulation of sex-specific gonad stem cell niche development by doublesex

 描述(由申请人提供)：性腺发育的一个关键方面是形成男性和女性性腺干细胞的壁龛。生殖系干细胞和体细胞干细胞都是连续产生配子发生所需的分化后代所必需的，而它们周围的微环境或“生态位”控制着性腺干细胞的分裂、维持和向分化的过渡。然而，性腺干细胞及其生态位在男性和女性中有很大的不同，有不同的调节控制和非常不同的结果(精子和卵子)。此外，在一些物种中，如哺乳动物，明确的干细胞群体只存在于男性中，而不存在于女性中，导致女性的生殖潜力更加有限。这项建议旨在了解性腺干细胞利基的性别特异性发育的机制。它涉及性别决定生物学的基本方面，这些方面也对干细胞生物学和人类生殖健康具有明显的影响。尽管启动性别决定的机制在不同的动物物种中差异很大，但现在人们意识到，一个单一的转录因子家族--双性相关转录因子(DMRT)--控制着大多数或所有动物物种的性二型性，包括苍蝇和人类。这些转录因子如何决定男性和女性性腺干细胞定位的差异尚不清楚。在这项提案中，我们将研究DMRT家族的创始成员双性果蝇(Drophila Doublesex，简称Dsx)是如何控制性腺干细胞利基中的性别二型性的。

 DESCRIPTION (provided by applicant): A critical aspect of gonad development is the formation of the male and female gonad stem cell niches. Both germline and somatic stem cells are required for continuous production of differentiated progeny for gametogenesis, while their surrounding microenvironments, or "niches", control gonad stem cell division, maintenance, and their transition into differentiation. However, gonad stem cells and their niches are very differen in males and females, with distinct regulatory control and very different outcomes (sperm vs. eggs). Further, in some species, such as mammals, a clear stem cell population exists only in males, but not in females, resulting in a more limited reproductive potential in females. This proposal aims to understand the mechanisms governing sex-specific development of the gonad stem cell niche. It addresses fundamental aspects of the biology of sex determination that also have clear implications for stem cell biology and human reproductive health. Although the mechanisms that initiate sex determination vary tremendously in different animal species, it is now appreciated that a single family of transcription factors, the "Doublesex, Mab3 Related Transcription Factors" (DMRTs), controls sexual dimorphism in the gonads of most or all animal species, including flies and humans. How these transcription factors dictate the differences between male and female gonad stem cell niches is not yet understood. In this proposal, we will investigate how the founding member of the DMRT family, Drosophila doublesex (dsx), controls sexual dimorphism in the gonad stem cell niche.