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

在新的资助期内，我们将利用我们从大型微阵列数据库中提取的信息 关注精原细胞成熟的过程以及维甲酸在这一过程中的作用。我们的阵列数据 清楚地确定了一个类维生素A反应基因，称为StraS，它在出生后的生殖细胞中表达。 雄性和雌性胚胎作为进入减数分裂的前体。在我们的实验室和其他工作 实验室已经证明，维生素A缺乏会阻碍未分化精原细胞的转化 A1精原细胞的分化。这一观察结果表明，视黄酸是必需的， 未分化的精原细胞进入分化途径并最终进入减数分裂。感应 StraS基因的缺失是这一过程的必要条件和可靠标记。视黄酸的作用， 随后发生的基因表达的变化极大地影响了精原细胞的成熟 以及减数分裂的开始拟议项目的主要部分是更明确地界定 精原细胞对视黄酸的反应，详细检查StraS基因的反应，并寻找其他基因 参与成熟过程。特别地，我们将关注另外3个基因的潜在作用， Tex13、Xlr4和EST号1700013H16Rik，它们都共享一种表达模式，该表达模式反映了 StraS。提出了三个具体目标：1。定义睾丸的视黄酸反应， 体细胞和精原细胞的成熟。2.定义调控StraS的转录元件 表达和精原细胞成熟。3.确定细胞定位和直接相互作用 StraS、Tex13、Xlr4和1700013H16Rik在精母细胞中的配体。该研究项目可以 潜在地决定启动雄性生殖细胞精子发生的分子机制。 关于维甲酸的作用和负责精原细胞进入的基因的知识， 这种分化途径可能导致避孕的新方法。

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.