Claire R. Cronmiller

The research in my lab was directed toward understanding how complex sequences of differentiation are genetically regulated during development. Drosophila oogenesis is being used as a model system for characterizing basic genetic and cell biological regulatory mechanisms that mediate the derivation, assembly and function of multicellular tissue structures. The specific experimental focus of the lab is the formation and maturation of the Drosophila ovarian follicle, and several approaches are being taken to study this developmental process. The first approach consists of elucidating the function and control of the multifunctional regulatory gene, daughterless (da), which provides an essential somatic function to control ovarian follicle formation. Follicle formation requires the directed migration and organization of mesodermally-derived somatic cells into a monolayer that envelops the developing germline, with individual adjacent follicles separated from each other by stalks of similarly derived somatic cells. This process of egg chamber morphogenesis is severely disrupted in da mutant genotypes. Discrete follicles rarely form, and the subsequent loss of follicle integrity results in complete sterility. The lab has shown genetically that da functions together with several other proteins whose biochemical identities suggest that intercellular signaling is critical during follicle morphogenesis. As a transcription factor, da protein in somatic cells probably responds to such signaling to ensure that sufficient somatic cells form to find their way around individual germline cysts and to differentiate into structurally functional follicle monolayers and interfollicular stalks. Using genetic and molecular approaches, we are currently (1) searching for targets that may be regulated by da protein during follicle formation, (2) looking for potential binding partners for the da protein, and (3) examining how da itself is regulated in a tissue-specific manner. The second approach involves exploiting the dose-sensitive requirement for da function during follicle formation. We have been using genetic interaction tests to identify other genes that make critical contributions to the same process, and we have focused especially on a gene, called stall, which appears from ovary transplantation experiments and clonal analysis to contribute to the regulation of ovarian follicle formation from outside the ovary. We are currently working toward identifying this gene molecularly. Finally, we have been developing Drosophila oogenesis as a model experimental system to study the effects of cocaine on development. Initially, we discovered that cocaine treatment leads to serious abnormalities in fly oogenesis, including follicle structural defects and follicle degeneration, and we have been using genetics, molecular biology and pharmacology to learn more about the cellular mechanisms of such cocaine-induced developmental defects. We anticipate that these studies with cocaine and other similar drugs will also help us uncover normal mechanisms of ovarian morphogenesis.