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bioRxiv · 10.1101/2019.12.13.875443

Sox8 and Sox9 act redundantly for ovarian-to-testicular fate reprogramming in the absence of Rspo1 in mouse sex reversal

Chaboissier, M.-C.·Richardson, N.·Gillot, I.·Gregoire, E. P.·Youssef, S. A.·de Rooij, D.·de Bruin, A.·De Cian, M.-C.
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Abstract

In mammals, testicular differentiation is initiated by transcription factors SRY and SOX9 in XY gonads, and ovarian differentiation involves R-spondin1 (RSPO1) mediated activation of WNT/{beta}-catenin signaling in XX gonads. Accordingly, the absence of RSPO1/Rspo1 in XX humans and mice leads to testicular differentiation and female-to-male sex reversal in a manner that does not require Sry or Sox9 in mice. Here we show that an alternate testis-differentiating factor exists and that this factor is Sox8. Specifically, genetic ablation of Sox8 and Sox9 prevents ovarian-to-testicular reprogramming observed in XX Rspo1 loss-of-function mice. Consequently, Rspo1 Sox8 Sox9 triple mutant gonads developed as atrophied ovaries. Thus, SOX8 alone can compensate for the loss of SOX9 for Sertoli cell differentiation during female-to-male sex reversal.

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Chaboissier, M.-C., Richardson, N., Gillot, I., Gregoire, E. P., Youssef, S. A., de Rooij, D., de Bruin, A., De Cian, M.-C.. 2019-12-16. Sox8 and Sox9 act redundantly for ovarian-to-testicular fate reprogramming in the absence of Rspo1 in mouse sex reversal. https://doi.org/10.1101/2019.12.13.875443

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