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Nat Commun. 2019 Nov 11;10(1):5116. doi: 10.1038/s41467-019-13060-1.

RUNX1 maintains the identity of the fetal ovary through an interplay with FOXL2.

Author information

1
Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, North Carolina, 27709, USA.
2
Integrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, North Carolina, 27709, USA.
3
Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S1085, F-35000, Rennes, France.
4
UMR BDR, INRA, ENVA, Université Paris Saclay, 78350, Jouy-en-Josas, France.
5
INRA, UR1037 Fish Physiology and Genomics, F-35000, Rennes, France.
6
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, 27710, USA.
7
Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, North Carolina, 27709, USA. humphrey.yao@nih.gov.

Abstract

Sex determination of the gonads begins with fate specification of gonadal supporting cells into either ovarian pre-granulosa cells or testicular Sertoli cells. This fate specification hinges on a balance of transcriptional control. Here we report that expression of the transcription factor RUNX1 is enriched in the fetal ovary in rainbow trout, turtle, mouse, goat, and human. In the mouse, RUNX1 marks the supporting cell lineage and becomes pre-granulosa cell-specific as the gonads differentiate. RUNX1 plays complementary/redundant roles with FOXL2 to maintain fetal granulosa cell identity and combined loss of RUNX1 and FOXL2 results in masculinization of fetal ovaries. At the chromatin level, RUNX1 occupancy overlaps partially with FOXL2 occupancy in the fetal ovary, suggesting that RUNX1 and FOXL2 target common sets of genes. These findings identify RUNX1, with an ovary-biased expression pattern conserved across species, as a regulator in securing the identity of ovarian-supporting cells and the ovary.

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