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. 2022 Sep 7;10:944776. doi: 10.3389/fcell.2022.944776

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Copyright © 2022 Nicol, Estermann, Yao and Mellouk.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Genetic regulation of pre-granulosa cell differentiation in birds. (A) In chickens, the pre-granulosa cells derive from a PAX2/OSR1/WNT4/DMRT1 positive mesenchymal cell population. During sex differentiation, they downregulate DMRT1 and PAX2 and start upregulating key pre-granulosa cell genes CYP19A1 and FOXL2. It is still unknown if these medullary pre-granulosa cells give rise to the granulosa cells in the adult ovary follicles. (B) Although WNT4 and OSR1 were identified as pre-granulosa cell genes, their functions have not been analyzed yet. FOXL2 and CYP19A1 downregulate Sertoli cell genes DMRT1, AMH and SOX9, inhibiting Sertoli cell differentiation and inducing pre-granulosa cell program. CYP19A1 is also known to regulate FOXL2 expression. Red: pro-ovarian genes/pathways; Blue: pro-testis genes/pathways; Plain arrow: direct effect; Dotted arrow: indirect effect.