10779/crick.12063747.v1 Silvana Guioli Silvana Guioli Debiao Zhao Debiao Zhao Sunil Nandi Sunil Nandi Michael Clinton Michael Clinton Robin Lovell-Badge Robin Lovell-Badge Oestrogen in the chick embryo can induce chromosomally male ZZ left gonad epithelial cells to form an ovarian cortex that can support oogenesis The Francis Crick Institute 2020 Chicken embryo Estrogen Gonadal chimera Ovary differentiation Sex determination Oestrogen Lovell-Badge FC001107 BRF-ack LM-ack 06 Biological Sciences 11 Medical and Health Sciences 2020-04-17 11:14:53 Journal contribution https://crick.figshare.com/articles/journal_contribution/Oestrogen_in_the_chick_embryo_can_induce_chromosomally_male_ZZ_left_gonad_epithelial_cells_to_form_an_ovarian_cortex_that_can_support_oogenesis/12063747 In chickens, the embryonic ovary differentiates into two distinct domains before meiosis: a steroidogenic core, the female medulla, overlain by the germ cell niche, the cortex. The differentiation of the medulla is a cell autonomous process based on chromosome sex identity (CASI). In order to address the extent to which cortex differentiation depends on intrinsic or extrinsic factors, we generated models of gonadal intersex by mixing ZW (female) and ZZ (male) cells in gonadal chimeras, or by altering estrogen levels of ZW and ZZ embryos. We found that CASI does not apply to the embryonic cortex. Both ZW and ZZ cells can form the cortex and this can happen independently of the phenotypic sex of the medulla as long as estrogen is provided. We also show that the cortex promoting activity of estrogen signalling is mediated via Estrogen Receptor alpha within the left gonad epithelium. However, the presence of a medulla with an "intersex" or male phenotype may compromise germ cells progression into meiosis, causing cortical germ cells to remain in an immature state in the embryo.