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.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 该项目的主要目标是了解原始生殖细胞(PGCs)的性别分化机制，原始生殖细胞是成人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PGCs开始具有双能，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控制，性腺体细胞是围绕原生殖细胞的细胞。但这一点还没有得到充分的检验。在性别分化后，男性和女性生殖细胞改变他们的DNA，并根据他们是否进入男性或女性特有的途径开始细胞分裂。这些特定性别的事件对于产生有功能的精子和卵子是必不可少的。否则，正常的受精和胚胎发育就不会正确发生。然而，我们不知道胎儿生殖细胞中性别分化和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，在受精后13.5天的小鼠中，PGCs控制着自己的命运，不再受周围体细胞的控制。在这个项目中，我们将首先研究在用外部化学物质/因子培养的生殖细胞中，性别分化与以下性别特异性事件之间的关系。下一步，我们将测试需要哪些条件，如果有的话，引导原生殖细胞进入男性或女性途径。最后，我们将确定在缺乏体细胞支持的情况下，生殖细胞是否保持自身进入减数分裂的内在时钟。