title: A critical time window of Sry action in gonadal sex determination in mice.
abstract: 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.
authors.affiliation: Department of Veterinary Anatomy, The University of Tokyo, Yayoi 1-1-1, Bunkyoku, Tokyo 113-8657, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Hiramatsu
authors.forename: Shogo
authors.initials: S
authors.lastname: Matoba
authors.forename: Masami
authors.initials: M
authors.lastname: Kanai-Azuma
authors.forename: Naoki
authors.initials: N
authors.lastname: Tsunekawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Katoh-Fukui
authors.forename: Masamichi
authors.initials: M
authors.lastname: Kurohmaru
authors.forename: Ken-Ichirou
authors.initials: K
authors.lastname: Morohashi
authors.forename: Dagmar
authors.initials: D
authors.lastname: Wilhelm
authors.forename: Peter
authors.initials: P
authors.lastname: Koopman
authors.forename: Yoshiakira
authors.initials: Y
authors.lastname: Kanai
mesh_terms: D000818:Animals; D005260:Female; D051525:Fibroblast Growth Factor 9 / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006066:Gonads / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009928:Organ Specificity; D055758:SOX9 Transcription Factor / Q000378:metabolism; D012708:Sertoli Cells / Q000166:cytology / Q000378:metabolism; D019849:Sex Determination Processes; D051876:Sex-Determining Region Y Protein / Q000235:genetics / Q000378:metabolism*; D013085:Spermatic Cord / Q000166:cytology / Q000196:embryology; D013997:Time Factors; D051153:Wnt Proteins / Q000378:metabolism; D060528:Wnt4 Protein
chemical_list: C496460:Fgf9 protein, mouse; D051525:Fibroblast Growth Factor 9; D055758:SOX9 Transcription Factor; D051876:Sex-Determining Region Y Protein; C527933:Sox9 protein, mouse; C497746:Sry protein, mouse; D051153:Wnt Proteins; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse