Conversion of an Esr1+ cell to Esr2+ cell during ovarian development

17β-estradiol (E2) is a steroid hormone that regulates a plethora of reproductive, metabolic, immunologic, cognitive, and skeletal functions. Two classical estrogen receptors, ESR1 (ERα) and ESR2 (ERβ) are responsible for the classical actions of E2 in mammalian species. In the ovary, ESR1 is localized to the surface epithelium and theca cells, whereas ESR2 is expressed in the granulosa cells. In previous studies, we have generated a transgenic mouse line that has an insertion of an enhanced Cre (iCre) recombinase in the exons of Esr1 and Esr2 gene, respectively. Esr1Cre mice can be used for deleting any floxed gene in the ESR1-expressing (Esr1+) cells, and Esr2Cre mice for excising genes in ESR2-expressing (Esr2+) cells. These novel transgenic mice are being used for lineage-tracing Esr1+ and Esr2+ cells and investigating unique roles that these estrogen receptors play in a single lineage. One interesting finding that we made is that Esr2+ granulosa cell seems to originate from cells that once expressed ESR1. I hypothesize that there is a molecular switch that convers Esr1+ cells to Esr2+ cells in developing ovary. In this project, 1) I will determine the temporal window when ESR1/ESR2 switching occurs, 2) the role of oocyte in granulosa cell lineage determination and 3) the mechanism of silencing Esr1 promoter during the transition of ESR1 to ESR2 granulosa cells. A discovery of the existence of a mechanism that converts ERa+ cells to ERb+ cells is expected to open-up a possibility of changing Esr1+ cells to Esr2+ cells.