The long term objective of this research is to learn about the events in early oogenesis that lead to the determination and differentiation of the oocyte and nurse cells. These events will be studied by analyzing three genes, fs(1)otu, fused and fs(2)B, that control development in the germarial cyst. Mutations in all three genes result in """"""""tumorous"""""""" egg chambers containing thousands of oogonial cells instead of the 16 interconnected cystocytes found in wild type ovaries. Genetic and morphological evidence suggests that they regulate the controlled mitotic divisions leading to the formation of the 16-celled germarial cyst. These genes will be cloned using a combination of hybrid-dysgenesis induced mutagenesis and chromosomal walking. They will be characterized at the molecular level, comparing the normal and mutant genes, the temporal and spatial distribution of RNAs transcribed from these genes, and the protein products encoded by them with the goal of learning how their functions influence early oogenesis. The mutant and wild type DNA comparisons will proceed at the level of restriction mapping, transcript mapping and, where indicated, sequence analysis. The RNA studies will be carried out using filter hybridizations and in situ hybridization to sectioned egg chambers. The protein studies outlined above will utilize the method of in vitro translation and polyacrylamide gel analysis. This project is related to health in several ways: 1) it explores the nature of mutations which cause sterility in females due to defects in early oogenesis, 2) it explores the controls of cell divisions and the causes for uncontrolled divisions leading to the formation of tumors.
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