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First published online 15 March 2005
doi: 10.1242/jcs.01738

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A novel Sry-downstream cellular event which preserves the readily available energy source of glycogen in mouse sex differentiation

¹ Department of Veterinary Anatomy, The University of Tokyo, Yayoi 1–1–1, Bunkyo-ku, Tokyo 113-8657, Japan
³ Department of Global Agricultural Sciences, The University of Tokyo, Yayoi 1–1–1, Bunkyo-ku, Tokyo 113-8657, Japan
² Department of Anatomy, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan

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

Accepted 18 January 2005

Sry is transiently activated in pre-Sertoli cells of the gonadal ridge to initiate testis differentiation in mice. In pre-Sertoli cells, however, the cellular events induced immediately after the onset of Sry expression remain largely unknown. Here we show that testis-specific glycogen accumulation in pre-Sertoli cells is one of the earliest cellular events downstream of Sry action. In developing XY gonads, glycogen accumulation starts to occur in pre-Sertoli cells from around 11.15 dpc (tail somite 14 stage) in a center-to-pole pattern similar to the initial Sry expression profile. Glycogen accumulation was also found in XX male gonads of Sry-transgenic embryos, but not in XX female gonads of wildtype embryos at any developmental stage. In vitro analyses using various culture conditions suggest that testis-specific glycogen deposition is a tissue-autonomous event that can be induced even in serum-free conditions and in a culture of gonadal explants without adjacent mesonephros. Moreover, glycogen accumulation in pre-Sertoli cells was significantly inhibited in vitro by the PI3K inhibitor LY294002, but not by the MEK inhibitor PD98059. Active phospho-AKT (PI3K effector) showed a high degree of accumulation in gonadal somatic cells of genital ridges in a testis-specific manner, both in vitro and in vivo. Therefore, these findings suggest that immediately after the onset of Sry expression, activation of the PI3K-AKT pathway promotes testis-specific glycogen storage in pre-Sertoli cells. To the best of our knowledge, this is a novel Sry-downstream cellular event which preserves this readily available energy source in Sertoli cells for testis-specific morphogenesis and hormone production.

Key words: Sry, Sox9, Glycogen, Sertoli cell, PI3K-AKT signaling, Sex differentiation

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