GENOMICS OF MALE GERM CELL SURVIVAL AND MAINTENANCE MECHANISMS

项目II：雄性生殖细胞生存和维持机制的基因组学 玛丽·安·汉德尔，项目负责人 减数分裂特别容易在前期I阶段中断和停滞，这是当两个关键的 正在发生的事件：染色体重组/突触和生殖细胞从基底层到基底层的传递 生精上皮腔内隔室，是促进减数分裂完成的环境。 尽管两种减数分裂重组事件都独立于生殖细胞和生精上皮 Sertoli细胞介导的事件是超过减数分裂前期的早期阶段所必需的， 大多数机制仍然知之甚少。再生基因组学计划产生的突变 为研究睾丸对早期减数分裂前期关键事件的调控提供机会。这个 Spcar1-4，sjsermatcell停滞1-4，突变导致早期和脆弱的前期停滞。 在目标1中，将使用以下方法确定生殖细胞减数分裂停滞的原因和后果 分子细胞学和基因表达分析技术。因为没有先验知识 无论这些突变是作用于生殖细胞还是作用于胞体导致精母细胞停滞，这都将是 通过精原干细胞(SSC)移植试验在AIM 2中解决。在Aim 3中，下游 将使用减数分裂停滞突变作为工具来研究突变对支持细胞的影响 研究细胞间的相互作用和对支持细胞成熟和睾丸至关重要的基因表达 差异化。为这些突变定义的基因组区域不包括任何已知的 参与减数分裂途径，确保这项工作将在目标4的分析中确定新的或 生殖细胞内的或外在的、对减数分裂必不可少的未知基因和机制 进步。这四个目标将共同解决不同减数分裂停滞表型的不同方面 影响减数分裂同一阶段的突变。 与公共卫生的相关性：通过发现控制早期减数分裂前期的新机制，这 这项工作将提供对常见的人类男性不育综合征和非整倍体起源的洞察。

Project II: Genomics of Male Germ Cell Survival and Maintenance Mechanisms Mary Ann Handel, Project Leader Meiosis is particularly vulnerable to interruption and arrest at prophase I stages, which is when two key events are occurring: chromosome recombination/synapsis and passage of germ cells from the basal to the adluminal compartment of the seminiferous epithelium, an environment that fosters completion of meiosis. Although both meiotic recombination events autonomous to the germ cell and seminiferous epithelium events mediated by the Sertoli cells are required for progress beyond this early stage of meiotic prophase, most of the mechanisms remain poorly understood. Mutations generated by the ReproGenomics Program provide opportunities to investigate the testicular regulation of critical events of early meiotic prophase. The spcar1-4, sjsermatocyte arrest 1-4, mutations cause arrest at this early and vulnerable stage of prophase. In Aim 1, the causes and consequences for the germ cell of meiotic arrest will be determined using techniques of molecular cytology and gene expression analysis. Because there is no a priori knowledge whether these mutations act in the germ cell or in the soma to cause spermatocyte arrest, this will be resolved in Aim 2 by spermatogonial stem cell (SSC) transplantation assays. In Aim 3, the downstream effects of the mutations on Sertoli cells will be investigated, using meiotic arrest mutations as a tool to examine aspects of cell-cell interactions and gene expression critical for Sertoli cell maturation and testis differentiation. The genomic regions defined for these mutations do not include any genes known to be involved in meiotic pathways, ensuring that this work will, in the analyses of Aim 4, identify new or unsuspected genes and mechanisms, either intrinsic or extrinsic to the germ cell, essential for meiotic progress. Together the four aims will tackle different aspects of the meiotic arrest phenotypes of different mutations affecting the same stage of meiosis. Relevance to Public Health: By discovery of novel mechanisms controlling early meiotic prophase, this work will provide insight into common human male infertility syndromes and the origins of aneuploidy.