Sox8 and Sox9 act redundantly for ovarian-to-testicular fate reprogramming in the absence of R-spondin1 in mouse sex reversals

Nainoa Richardson, Isabelle Gillot, Elodie P. Gregoire, Sameh A. Youssef, Dirk de Rooij, Alain de Bruin, Marie-Cecile De Cian, Marie-Christine Chaboissier*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    2 Citations (Scopus)
    31 Downloads (Pure)

    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 requireSry 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.

    Original languageEnglish
    Article number53972
    Pages (from-to)1-19
    Number of pages19
    JournaleLife
    Volume9
    DOIs
    Publication statusPublished - 26-May-2020

    Keywords

    • TRANSCRIPTION FACTOR SOX10
    • CAMPOMELIC DYSPLASIA
    • BETA-CATENIN
    • TARGET GENES
    • SRY
    • DIFFERENTIATION
    • MICE
    • EXPRESSION
    • MUTATIONS
    • BINDING

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