A critical time window of Sry action in gonadal sex determination in mice.
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.
Hiramatsu
Ryuji
R
Department of Veterinary Anatomy, The University of Tokyo, Yayoi 1-1-1, Bunkyoku, Tokyo 113-8657, Japan.
Matoba
Shogo
S
Kanai-Azuma
Masami
M
Tsunekawa
Naoki
N
Katoh-Fukui
Yuko
Y
Kurohmaru
Masamichi
M
Morohashi
Ken-Ichirou
K
Wilhelm
Dagmar
D
Koopman
Peter
P
Kanai
Yoshiakira
Y
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
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