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First published online 26 November 2008
doi: 10.1242/dev.029587

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

¹ Department of Veterinary Anatomy, The University of Tokyo, Yayoi 1-1-1, Bunkyoku, Tokyo 113-8657, Japan.
² Department of Anatomy, Kyorin University School of Medicine, Shinkawa 6-20-2, Mitaka, Tokyo 181-8611, Japan.
³ Department of Aging Intervention, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Gengo 36-3, Morioka-cho, Obu, Aichi 474-8511, Japan.
⁴ Department of Molecular Biology, Graduate School of Medicine, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan.
⁵ Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia.

^* Author for correspondence (e-mail: aykanai{at}mail.ecc.u-tokyo.ac.jp)

Accepted 23 October 2008

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.

Key words: Sry, Sox9, Fgf9, Wnt4, Sertoli cells, Sex differentiation, Mouse

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