Sertoli cell differentiation is induced both cell-autonomously and through prostaglandin signaling during mammalian sex determination

Dagmar Wilhelm, Fred Martinson, Stephen Bradford, Megan J. Wilson, Alexander N. Combes, Annemiek Beverdam, Josephine Bowles, Hirofumi Mizusaki, Peter Koopman

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235 Citations (Scopus)


We have raised an antibody specifically recognizing endogenous mouse SRY protein and used it to investigate the molecular and cellular mode of action of SRY in testis determination. We find that expression of SRY protein closely mirrors the expression of Sry mRNA in mouse genital ridges and is detectable for 6 to 8 h after the mRNA ceases to be detectable. The subset of somatic cells that expresses SRY begins to express SOX9 almost immediately. Since these SOX9-positive cells go on to develop as Sertoli cells, it appears that SRY expression marks the pre-Sertoli cell lineage and leads to up-regulation of Sox9 expression cell-autonomously. However, a small proportion of SOX9-positive cells did not appear to express SRY, possibly reflecting the additional involvement of paracrine signaling in activating Sox9 transcription in these cells. We confirmed by ex vivo cell mixing experiments that SRY is able to engage receptor-mediated signaling to up-regulate Sox9 expression. Finally, we showed by employing specific inhibitors that the causative signaling molecule is prostaglandin D2 (PGD2) and that PGD2 can induce Sox9 transcription in cultured XX gonads. Our data indicate a mechanism whereby Sry uses both a cell-autonomous mechanism and a PGD2-mediated signaling mechanism to stimulate expression of Sox9 and induce the differentiation of Sertoli cells in vivo.

Original languageEnglish
Pages (from-to)111-124
Number of pages14
JournalDevelopmental Biology
Issue number1
Publication statusPublished - 1 Nov 2005
Externally publishedYes


  • Gonad development
  • Prostaglandin
  • Sertoli cell
  • Sex determination
  • Sox9
  • SRY
  • Testis differentiation

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