Genetic analysis of ovary development and oogenesis

描述(申请人提供)：卵子发生将生殖细胞转化为卵母细胞，卵母细胞通过输卵管后成为受精卵。卵子发生的过程在无脊椎动物模式生物中得到了很好的研究，许多方面的特点是明确的分子途径，最初是通过功能丧失的研究来定义的。在脊椎动物中，卵子发生得到了很好的描述，但对其调控的分子机制知之甚少。多种因素已被证明在小鼠卵子发生中起作用；然而，分子途径尚未详细阐述。只有一个或几个因素被确定为调节卵子发生的特定阶段，这表明有无数缺失的因素。我们建议在斑马鱼中产生卵巢/卵子发生突变的资源来研究脊椎动物的卵子发生，这是一种补充其他脊椎动物卵子发生的方法。由于卵子发生的大部分方面在哺乳动物和斑马鱼之间是保守的，斑马鱼卵巢/卵子发生突变的集合，结合它们的特征和突变基因的分子鉴定，将为脊椎动物卵子发生仍然鲜为人知的过程提供丰富的分子途径。具体地说，我们建议分离斑马鱼卵子发生和卵巢发育所需基因的隐性突变。将对突变体进行特征鉴定，以确定表型的性质和扰乱的生物过程。最后，卵子发生突变将被映射到染色体位置，以便于种群的繁殖，并作为鉴定突变基因的分子性质的起点。斑马鱼的这种卵巢/卵子发生筛选将导致发现参与卵子发生的方方面面的基因，从原始卵泡发育到卵母细胞成熟和排卵。预计这些研究将与理解人类生殖障碍直接相关。斑马鱼突变基因的鉴定将提供导致人类缺陷的候选基因，这最终可能导致基因测试或治疗干预。

DESCRIPTION (provided by applicant): Oogenesis transforms germ cells into oocytes, which following passage through the oviduct, become fertilizable eggs. The process of oogenesis is well studied in invertebrate model organisms with many aspects characterized by well-defined molecular pathways, first defined through loss-of-function studies. In vertebrates, oogenesis is well described, however, little is known about the molecular mechanisms regulating it. Multiple factors have been shown to function in mouse oogenesis; however, molecular pathways have not yet been elaborated. Only single, or a few, factors have been identified that regulate particular stages of oogenesis, indicating a myriad of missing factors. We propose to generate a resource of ovary/oogenesis mutants in the zebrafish to study vertebrate oogenesis, an approach complementary to those in other vertebrates. Since most aspects of oogenesis are conserved between mammals and zebrafish, a collection of ovary/oogenesis mutants in zebrafish, in conjunction with their characterization and the molecular identification of the genes mutated, will provide a wealth of molecular inroads to the still poorly understood process of vertebrate oogenesis. Specifically, we propose to isolate recessive mutations in genes required in the zebrafish for oogenesis and ovary development. The mutants will be characterized to determine the nature of the phenotype and the biological process disrupted. Lastly, the oogenesis mutations will be mapped to chromosomal positions to facilitate propagating the stock and as a starting point to identify the molecular nature of the mutated gene. This ovary/oogenesis screen in the zebrafish will lead to the discovery of genes involved in all aspects of oogenesis from primordial follicle development to oocyte maturation and ovulation. These studies are expected to be directly relevant to the understanding of human reproductive disorders. Identification of the mutant zebrafish genes will provide candidate genes responsible for the human defects, which could ultimately lead to genetic testing or therapeutic intervention.