MECHANISMS OF SEX DIFFERENTIATION IN MOUSE FETAL GERM CELLS

小鼠胎儿生殖细胞性别分化的机制

• 批准号: 8360320
• 负责人: YUKIKO YAMAZAKI
• 金额: $ 22.21万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360320
• 关键词: Adult; Beginning of Life; Biogenesis; Cell Culture Techniques; Cell division; Cells; Centers of Research Excellence; Chemicals; DNA; Data; Embryo; Embryonic Development; Event; Female; Fertilization; Funding; Germ Cells; Goals; Grant; Institutes; Meiosis; Mus; National Center for Research Resources; Pathway interactions; Principal Investigator; Research; Research Infrastructure; Resources; Sex Differentiation; Somatic Cell; Source; Structure of primordial sex cell; Testing; United States National Institutes of Health; base; blastomere structure; cost; egg; fetal; male; sex; sperm cell

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The primary goal of project is to understand the mechanisms of sex differentiation in primordial germ cells (PGCs), the embryonic cells that give rise to either sperm or egg cells in the adult. Current evidence suggests that PGCs in both female (XX) and male (XY) embryos begin life being bipotent, capable of differentiating along either the male or female pathway. The decision to differentiate to male or female germs cells is controlled by the gonadal somatic cells, the cells that surround the PGCs. But this has not been fully tested. After sex differentiation, male and female germ cells alter their DNA and begin cell division based on whether they have entered the male or female specific pathway. These sex-specific events are essential to produce functional sperm and eggs. Otherwise, normal fertilization and embryonic development do not occur correctly. However, we do not know the exact relationship between sex differentiation and the following sex-specific events in fetal germ cells. Our previous data demonstrate that in mice by 13.5 days after fertilization, PGCs control their own fate, and are no longer regulated by the surrounding somatic cells. In this project, we will first examine the relationship between sex differentiation and the following sex-specific events in germ cells cultured with external chemicals/factors. Next, we will test which conditions, if any, are required to direct PGCs into male or female pathway. Finally, we will determine if germ cells maintain intrinsic clock to enter meiosis by themselves in the absence of somatic support.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 该项目的主要目标是了解原始生殖细胞（PGC）性别分化的机制，原始生殖细胞是在成人中产生精子或卵细胞的胚胎细胞。 目前的证据表明，雌性 (XX) 和雄性 (XY) 胚胎中的 PGC 在生命开始时都是双能的，能够沿着雄性或雌性途径分化。 分化为雄性或雌性生殖细胞的决定由性腺体细胞（PGC 周围的细胞）控制。 但这还没有经过充分测试。 性别分化后，雄性和雌性生殖细胞会改变其 DNA，并根据是否进入雄性或雌性特定途径开始细胞分裂。这些性别特异性事件对于产生功能性精子和卵子至关重要。 否则，正常的受精和胚胎发育就不会正确发生。 然而，我们不知道性别分化与胎儿生殖细胞中以下性别特异性事件之间的确切关系。 我们之前的数据表明，在小鼠受精后 13.5 天，PGC 控制自己的命运，不再受到周围体细胞的调节。 在这个项目中，我们将首先检查用外部化学物质/因子培养的生殖细胞中的性别分化和以下性别特异性事件之间的关系。 接下来，我们将测试将 PGC 引导至男性或女性途径所需的条件（如果有）。 最后，我们将确定生殖细胞在没有体细胞支持的情况下是否维持内在时钟以自行进入减数分裂。