Retinoic Acid, Stra8, & Key Factors in Spermatogonia Maturation & Testis Function

在新的资助期内，我们将利用从我们的大型微阵列数据库中提取的信息 重点介绍精原细胞成熟的过程以及维甲酸在这一过程中的作用。我们的数组数据 明确识别在出生后的生殖细胞中表达的维甲酸反应基因，称为STRAS 雄性和胚胎雌性作为进入减数分裂的前驱。我们实验室和其他实验室以前的工作 实验室表明，缺乏维生素A会阻碍未分化精原细胞的转化 分化为A1精原细胞。这一观察结果表明，维甲酸是 未分化的精原细胞进入分化途径，最终进入减数分裂。归纳 STRAS是这一过程所必需的，也是一个可靠的标记。维甲酸和维甲酸的作用 随后发生的基因表达的变化，极大地影响精原细胞的成熟 以及减数分裂的开始。拟议项目的主要部分是为了更清楚地定义 精原细胞对维甲酸的反应，详细检测STRAS基因的反应并寻找其他基因 参与了成熟过程。特别是，我们将重点关注另外3个基因的潜在作用， Tex13、Xlr4和EST no.1700013H16Rik都共享一个反映了 斯特拉斯。提出了三个具体目标：1.定义睾丸对维甲酸的反应 体细胞和精原细胞的成熟。2.定义调控STRAS的转录元件 表达和精原成熟。3.确定细胞定位和直接相互作用 Stras、Tex13、Xlr4和1700013H16Rik在精母细胞中的配对。这项研究项目可能 潜在地确定了在雄性生殖系中启动精子发生的分子机制。 维甲酸的作用和精原细胞进入精原细胞的基因的知识 这种分化途径可能会带来新的避孕方法。

In the new grant period we will utilize the information we have extracted from our large microarray databases to focus on the process of spermatogonial maturation and the role of retinoids in that process. Our array data clearly identifies a retinoid responsive gene, termed StraS, that is expressed in germ cells of the postnatal male and embryonic female as a precursor to entry into meiosis. Previous work in our laboratory and other laboratories has shown that a vitamin A deficiency blocks the conversion of undifferentiated spermatogonia to differentiating A1 spermatogonia. This observation suggests retinoic acid is required for the undifferentiated spermatogonia to enter into a differentiation pathway and ultimately into meiosis. Induction of the gene, StraS, is a requirement and a reliable marker for this process. The action of retinoic acid and the subsequent changes in gene expression that occur, dramatically impact the maturation of spermatogonia and the onset of meiosis. Major parts of the proposed project are to more clearly define the response of spermatogonia to retinoic acid, to examine the response of the StraS gene in detail and to find other genes involved in the maturation process. In particular, we will focus on the potential role of 3 additional genes, Tex13, Xlr4 and an EST no. 1700013H16Rik which all share a pattern of expression that mirrors that of StraS. Three specific aims are proposed: 1. Define the retinoic acid response of the testis with regard to the somatic cells and the maturation of spermatogonia. 2. Define the transcriptional elements that regulate StraS expression and spermatogonial maturation. 3. Determine the cellular localization and direct interacting partners of StraS, Tex13, Xlr4 and 1700013H16Rik in spermatocytes. This research project could potentially determine the molecular mechanisms that initiate spermatogenesis in the male germline. Knowledge about the actions of retinoic acid and the genes responsible for the entry of spermatogonia into the differentiation pathway could lead to new approaches to contraception.