PROJECT 2: TRANSLATIONAL REGULATION OF THE MEIOTIC CELL CYCLE IN THE MALE.

项目 2：男性减数分裂细胞周期的翻译调控。

• 批准号: 8638813
• 负责人: MARGARET T FULLER
• 金额: $ 33.1万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8638813
• 关键词: 3' Untranslated Regions; B-Lymphocytes; Binding; Biological Models; Cell Cycle; Cell Cycle Progression; Cell Cycle Regulation; Cell Differentiation process; Cells; Chromosomes; Cis-Acting Sequence; Collaborations; Cyclin B; DNA biosynthesis; Development; Drosophila genus; Embryo; Embryonic Development; Eukaryota; Event; Family; Family member; G2 Phase; G2/M Transition; Gametogenesis; Gene Expression; Genetic; Germ Cells; Heterogeneous-Nuclear Ribonucleoproteins; Homologous Gene; Homologous Protein; Human; Hybrids; In Vitro; Infertility; Maps; Meiosis; Molecular; Molecular Analysis; Oocytes; Oogenesis; Organism; Play; Poly(A)-Binding Proteins; Polyadenylation; Production; Prophase; Proteins; RNA; RNA Cap-Binding Proteins; RNA-Binding Proteins; Recruitment Activity; Regulation; Reproduction; Reproductive Biology; Role; Specific qualifier value; Spermatocytes; Spermatogenesis; Spermiogenesis; Staging; Synapses; Testing; Time; Transcript; Translational Regulation; Translational Repression; Translations; Universities; Work; Yeasts; base; cdc25 Phosphatase; cell type; design; egg; gene discovery; insight; male; men; oocyte maturation; premature; prevent; programs; sex; stem cell biology

Meiosis is the signature event of the germ cell developmental program, absolutely required for sexual reproduction eukaryotes. Proper regulation of meiotic progression is crucial for production of functional gametes. A key aspect of meiosis is a germ cell specific cell cycle, in which a final round of DNA synthesis (premeiotic S) is followed by a greatly extended G2, termed meiotic prophase, prior to the two meiotic divisions. This signature cell cycle delay provides critical time for homologous chromosomes to pair, synapse and recombine, as well as for major biosynthetic events that drive gamete differentiation. In oocytes, the transcriptional, translational and morphogenetic changes that produce the egg and prepare for early embryogenesis are largely accomplished during meiotic prophase. In male germ cells, although dramatic morphological changes that produce mature gametes occur after the meiotic divisions, a major part of the gene expression program that sets up spermiogenesis takes place during meiotic prophase. In both sexes, meiotic onset, progression, maturation, and activation of the meiotic divisions are key regulatory points. Understanding how these events are regulated is key for understanding the molecular basis of meiotic arrest infertility, for designing effective strategies for differentiating germ cells from embryonic precursors, and for developing and maturing competent gametes in vitro. The analysis proposed in this subproject of the U54 Cooperative Center for Reproductive and Stem Cell Biology will elucidate fundamental mechanisms that control the cell cycle for meiotic prophase, including the critical control circuits that first pause the cell cycle, then finally activate the G2/M transition for meiosis I once proper expression of the program for gametogenesis has been achieved.

减数分裂是生殖细胞发育程序的标志性事件，是性行为的绝对必要条件。 生殖真核生物减数分裂进程的适当调节对于功能性细胞的产生是至关重要的。 配子减数分裂的一个关键方面是生殖细胞特异性细胞周期，其中最后一轮DNA合成 （减数分裂前S）之后是一个大大延长的G2，称为减数分裂前期，在两次减数分裂之前 分裂这种标志性的细胞周期延迟为同源染色体配对、突触 和重组，以及驱动配子分化的主要生物合成事件。在卵母细胞中， 转录，翻译和形态发生的变化，产生卵子，并准备早期 胚胎发生主要在减数分裂前期完成。在男性生殖细胞中，虽然戏剧性的 产生成熟配子的形态变化发生在减数分裂之后，这是基因的主要部分。 建立精子发生的表达程序发生在减数分裂前期。在两性中，减数分裂 减数分裂的开始、进行、成熟和激活是关键的调节点。理解 这些事件是如何被调节的是理解减数分裂停滞不育的分子基础的关键， 设计从胚胎前体分化生殖细胞的有效策略， 在体外使有能力的配子成熟。U 54合作中心的这一分项目中提出的分析 生殖和干细胞生物学将阐明控制细胞周期的基本机制， 减数分裂前期，包括首先暂停细胞周期，然后最终激活细胞周期的关键控制电路。 一旦配子发生程序的正确表达完成，减数分裂I的G2/M转换。