Sexual development of the Drosophila gonad

项目摘要 性腺中的性二型性对于生殖细胞的正常发育和有性繁殖是至关重要的。 繁殖。在果蝇中，睾丸和卵巢都有生殖系干细胞群体， 它们受各自的干细胞生态位调控，是持续产生配子所必需的。 生殖系干细胞的形成需要生殖细胞和体细胞性腺之间的特定相互作用， 生殖系干细胞和它们的生态位在雄性和雌性之间都表现出了重要的差异。这 在其他物种中也是如此，例如哺乳动物，在这些物种中，雄性和雌性在 它们形成生殖系干细胞的能力。这项建议的重点是了解利基和 生殖系干细胞是在发育过程中形成的，在生殖细胞和胞体中如何进行性别鉴定 共同努力控制利基干细胞和生殖系干细胞中的性别二型性。 我们将首先研究钙粘附素在巢干细胞和生殖系干细胞形成中的作用。去- 钙粘蛋白和dN-钙粘蛋白在发育中的生殖系干细胞巢中表达，在雄性和 雌性，并定位于壁龛和生殖系干细胞之间的界面。我们会调查的 这些细胞间的黏附分子是否对壁龛的形态发生和 调节生殖系干细胞的行为。其次，我们将研究男性与男性的形成过程。 雌性的生态位受关键的性别决定因子双性(Dsx)的调节。我们的初步数据 这表明，DsX调节了生态位中的性别二型性，并且雄性生态位可能能够反式- 分化形成雌性生态位。我们将研究dsx如何影响性腺中的生态位形成。 发展。第三，我们将研究生殖细胞中的性别决定如何与特定性别的 胞体控制生殖细胞发育和生殖系干细胞的形成。在苍蝇和哺乳动物中， 生殖细胞的性别必须与体细胞的性别相匹配，才能正常发育生殖细胞和生育能力。我们 将调查为什么生殖细胞不能对异性的胞体做出适当的反应。最后，我们会 研究一种新基因--不让孩子掉队(NCLB)--在男性生殖系干细胞发育中的作用。 NCLB在雄性生殖细胞成为生殖系干细胞时表达，并且NCLB突变体 表现出男性生殖系干细胞的严重丧失。我们的数据表明NCLB蛋白是一种染色质- 相关因素，我们将检验NCLB是适当的表观遗传控制所必需的假设 雄性生殖系干细胞发育。 拟议的工作将进一步加深我们对体节和性别化发育的理解 生殖细胞相互作用以控制生殖系干细胞的形成。这项工作对我们的 了解人类的性发育和生育能力，以及如何成年这一更广泛的问题 干细胞发育，并受其利基环境的调节。

Project Summary The creation of sexual dimorphism in the gonad is critical for proper germ cell development and sexual reproduction. In Drosophila, both the testis and ovary have germline stem cell populations that are regulated by their respective stem cell niches and are essential for continuous production of gametes. Germline stem cell formation requires specific interactions between the germ cells and somatic gonad, and both the germline stem cells and their niches exhibit important differences in males and females. This is also true in other species, such as mammals, where the male and female exhibit clear differences in their ability to form germline stem cells. This proposal focuses on understanding how the niches and germline stem cells are formed during development, and how sexual identity in the germ cells and soma work together to control sexual dimorphism in the niche and germline stem cells. We will first study the role of the cadherins in the formation of the niche and germline stem cells. DE- cadherin and DN-cadherin are expressed in the developing germline stem cell niche in both males and females, and are localized to the interface between the niche and germline stem cells. We will investigate whether these cell-cell adhesion molecules are important for morphogenesis of the niche and for regulating the behavior of the germline stem cells. Second, we will study how the formation of the male vs. female niche is regulated by the critical sex determination factor doublesex (dsx). Our preliminary data indicate that dsx regulates sexual dimorphism in the niche and that the male niche may be able to trans- differentiate to form the female niche. We will study how dsx influences niche formation during gonad development. Third, we will study how sex determination in the germ cells interacts with a sex-specific soma to control germ cell development and germline stem cell formation. In flies, as well as mammals, the sex of the germ cells must match the sex of the soma for proper germ cell development and fertility. We will investigate why germ cells fail to respond appropriately to a soma of a different sex. Finally, we will investigate the role of a new gene, no child left behind (nclb), in male germline stem cell development. nclb is expressed in male germ cells at the time they become germline stem cells, and nclb mutants exhibit a severe loss of male germline stem cells. Our data indicate that the NCLB protein is a chromatin- associated factor and we will test the hypothesis that NCLB is required for proper epigenetic control of male germline stem cell development. The proposed work will further our understanding of how sex-specific development of the soma and germ cells interact to control germline stem cell formation. This work has clear implications for our understanding of human sexual development and fertility, as well as the broader question of how adult stem cells develop and are regulated by their niches.