Molecular and genetic analysis of sex determination in Drosophila

我们的长期目标是研究果蝇性发育的遗传控制的分子机制。由于性别决定途径中的许多基因都受到RNA加工的调控，这些研究也将有助于我们理解选择性RNA剪接作为基因调控的一种手段。我们的研究重点是sans-fille(Snf)基因。遗传学研究表明，SNF在生殖系和胞体的性决策过程中都发挥着关键作用。为了进一步了解这个新发现的基因，我们建议：1)通过分析该基因座的零等位基因，来确定SNF是否是性别决定所必需的，或者它在发育过程中是否具有更普遍的功能。2)对SNF基因及其产物进行详细的分子鉴定；3)采用分子和遗传学相结合的方法，将SNF置于性别决定基因的调控层次中。在果蝇中，具有X和Y染色体的果蝇个体发育成雄性果蝇，而具有2X染色体的果蝇个体发育成雌性果蝇。采用哪种发育途径的决定是在胚胎生命期间由胚胎体内的每个细胞做出的。我们从本世纪初就知道，细胞通过计算它们所包含的X染色体的数量来做出决定，但直到过去十年，人们才阐明了做出决定的机制的更多细节。这是一项研究最近发现的这一机制的早期步骤的提议。

Our long term goal is to investigate the molecular mechanisms underlying the genetic control of sexual development in Drosophila. Because many of the genes in the sex determination pathway are regulated by RNA processing, these studies will also contribute to our understanding of alternative RNA splicing as a means of gene regulation. Our research is focused on the sans-fille (snf) gene. Genetic studies suggest that snf plays a key role in the sexual decision making process in both the germline and the soma. To further our understanding of this newly identified gene we propose: 1) To determine whether snf is required only for sex determination or whether it has a more generalized function in development by analyzing null alleles of the locus. 2) To initiate a detailed molecular characterization of the snf gene and its products and 3) To place snf in the regulatory hierarchy of sex determination genes by a combined molecular and genetic approach. In the fruit fly Drosophila individuals with an X and a Y chromosome develop into males and those with 2X chromosomes develop into females. The decision of which developmental pathway to adopt is made during embryonic life by every cell in the body of the embryo. We have known since the early years of this century that the cells make their decision by counting the number of X chromosomes they contain, but it is only over the past decade that more of the details of the mechanism by which the decision is made have been elucidated. This is a proposal to study a recently discovered early step in this mechanism.