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雄性和雌性性腺干细胞龛的形成。生殖系干细胞和体细胞干细胞都是持续产生配子发生的分化后代所必需的，而它们周围的微环境或“小生境”控制着性腺干细胞的分裂、维持以及它们向分化的过渡。然而，性腺干细胞和它们的小生境在男性和女性中非常相似，具有不同的调节控制和非常不同的结果（精子与卵子）。此外，在一些物种中，例如哺乳动物，明确的干细胞群体仅存在于雄性中，而不存在于雌性中，导致雌性的生殖潜力更有限。该建议旨在了解性腺干细胞龛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，也对干细胞生物学和人类生殖健康有明显的影响。尽管启动性别决定的机制在不同的动物物种中差异巨大，但现在认识到，转录因子的单个家族，“Doublemex，Mab3相关转录因子”（DMRTs），控制大多数或所有动物物种（包括苍蝇和人类）的性腺中的性二型性。这些转录因子是如何决定男性和女性性腺干细胞龛之间的差异还不清楚。在这个建议中，我们将调查DMRT家族的创始成员，Drosophila doublesex（dsx），如何控制性腺干细胞龛中的性二态性。

 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.