A critical time window of Sry action in gonadal sex determination in mice

Ryuji Hiramatsu, Shogo Matoba, Masami Kanai-Azuma, Naoki Tsunekawa, Yuko Katoh-Fukui, Masamichi Kurohmaru, Ken Ichirou Morohashi, Dagmar Wilhelm, Peter Koopman, Yoshiakira Kanai

Research output: Contribution to journalArticlepeer-review

173 Citations (Scopus)


In mammals, the Y-linked sex-determining gene Sry cell-autonomously promotes Sertoli cell differentiation from bipotential supporting cell precursors through SRY-box containing gene 9 (Sox9), leading to testis formation. Without Sry action, the supporting cells differentiate into granulosa cells, resulting in ovarian development. However, how Sry acts spatiotemporally to switch supporting cells from the female to the male pathway is poorly understood. We created a novel transgenic mouse line bearing an inducible Sry transgene under the control of the Hsp70.3 promoter. Analysis of these mice demonstrated that the ability of Sry to induce testis development is limited to approximately 11.0-11.25 dpc, corresponding to a time window of only 6 hours after the normal onset of Sry expression in XY gonads. If Sry was activated after 11.3 dpc, Sox9 activation was not maintained, resulting in ovarian development. This time window is delimited by the ability to engage the high-FGF9/low-WNT4 signaling states required for Sertoli cell establishment and cord organization. Our results indicate the overarching importance of Sry action in the initial 6-hour phase for the female-to-male switching of FGF9/WNT4 signaling patterns.

Original languageEnglish
Pages (from-to)129-138
Number of pages10
Issue number1
Publication statusPublished - 2009

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology


Dive into the research topics of 'A critical time window of Sry action in gonadal sex determination in mice'. Together they form a unique fingerprint.

Cite this