The sex-determining factors SRY and SOX9 regulate similar target genes and promote testis cord formation during testicular differentiation

Cell Rep. 2014 Aug 7;8(3):723-33. doi: 10.1016/j.celrep.2014.06.055. Epub 2014 Jul 31.


Male sex determination is mediated sequentially by sex-determining region Y (SRY) and related SRY-box 9 (SOX9) transcription factors. To understand the gene regulatory hierarchy for SRY and SOX9, a series of chromatin immunoprecipitation and whole-genome promoter tiling microarray (ChIP-Chip) experiments were conducted with mouse gonadal cells at the time of sex determination. SRY and SOX9 bind to the promoters of many common targets involved in testis differentiation and regulate their expression in Sertoli cells. SRY binds to various ovarian differentiation genes and represses their activation through WNT/β-catenin signaling. Sertoli cell-Sertoli cell junction signaling, important for testis cord formation, is the top canonical pathway among the SRY and SOX9 targets. Hence, SRY determines Sertoli cell fate by repressing ovarian and activating testicular differentiation genes, promotes early Sertoli cells to form testis cord, and then passes on its functions to SOX9, which regulates common targets and activates its own gene regulatory program, beyond SRY actions, in sex determination.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation
  • Female
  • Gene Expression Regulation, Developmental
  • Male
  • Mice
  • SOX9 Transcription Factor / genetics
  • SOX9 Transcription Factor / metabolism*
  • Sertoli Cells / cytology*
  • Sertoli Cells / metabolism
  • Sex Determination Processes*
  • Sex-Determining Region Y Protein / genetics
  • Sex-Determining Region Y Protein / metabolism*
  • Wnt Signaling Pathway


  • SOX9 Transcription Factor
  • Sex-Determining Region Y Protein
  • Sox9 protein, mouse