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. ? ?
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