9419613 Johnson This proposal describes studies to evaluate physiological mechanisms that mediate normal cell death (a process called apoptosis or programmed cell death) within preovulatory ovarian follicles of the domestic chicken. Although in most animal species follicle atresia (the death and resorption of nonviable follicles) occurs in greater than 95% of ovarian follicles present within the ovary at the time of hatch (or birth), relatively little is known about events within follicle cells that are associated with the initiation of follicle death. Dr. Johnson was among the first to determine that ovarian follicle atresia in the hen, as well as in mammals, is mediated via the process of apoptosis thus providing for the first time an early endpoint to facilitate studying causative effects. Among the physiological factors now known to be associated with cell survival/cell death in a variety of mammalian and avian tissues are members of the bc1-2 gene family (a family of genes related to Ced genes previously characterized in the worm, Caenorhabditis elegans). The fact that these genes are so highly conserved during the process of evolution points to the importance of their function in maintaining cell viability or, alternatively, inducing cell death. Thus, results from the studies outlined will have implications for better understanding the cellular and molecular mechanisms which regulate ovarian follicle selection and physiological follicle death in nonmammalian species. Moreover, the data should more generally provide information related to the regulation and mechanisms responsible for physiological cell death in all tissues from vertebrate species. ***