Despite its importance to the continuation of species, the differentiation of primordial germ cells into functional oocytes is poorly understood. Primordial germ cells begin to differentiate into oocytes during embryonic development in the mouse. The oocytes develop in clusters called germline cysts, a conserved phase of oocyte development in both vertebrates and invertebrates. During late fetal and early neonatal development, mouse germ cell cysts break apart into single oocytes (cyst breakdown) that become surrounded by pre-granulosa cells to form primordial follicles (follicle formation). During the process of cyst breakdown, a subset of cells in each cyst die with only a third of the initial number of oocytes surviving to form primordial follicles. The mechanisms that control cyst breakdown, oocyte survival and follicle assembly are currently unknown. However, recent work suggests estrogen signaling may play an important role in maintaining oocytes in cysts. The project goal is to understand the role of estrogen signaling in cyst breakdown and primordial follicle formation. Establishing the role of estrogen signaling in neonatal oocyte differentiation will elucidate mechanisms leading to formation of the primordial follicle pool. This work will to contribute to our knowledge of conserved mechanisms of germ cell differentiation and lead to a better understanding of mammalian infertility. In addition to its impact on ovarian function, the project will foster education and training through active participation of both undergraduate and graduate students. Community outreach will be achieved by revival of a program that brings together scientists and nonscientists in the community and by participation in a local science program for high school girls.