title: SOX9 regulates microRNA miR-202-5p/3p expression during mouse testis differentiation.
abstract: MicroRNAs are important regulators of developmental gene expression, but their contribution to fetal gonad development is not well understood. We have identified the evolutionarily conserved gonadal microRNAs miR-202-5p and miR-202-3p as having a potential role in regulating mouse embryonic gonad differentiation. These microRNAs are expressed in a sexually dimorphic pattern as the primordial XY gonad differentiates into a testis, with strong expression in Sertoli cells. In vivo, ectopic expression of pri-miR-202 in XX gonads did not result in molecular changes to the ovarian determination pathway. Expression of the primary transcript of miR-202-5p/3p remained low in XY gonads in a conditional Sox9-null mouse model, suggesting that pri-miR-202 transcription is downstream of SOX9, a transcription factor that is both necessary and sufficient for male sex determination. We identified the pri-miR-202 promoter that is sufficient to drive expression in XY but not XX fetal gonads ex vivo. Mutation of SOX9 and SF1 binding sites reduced ex vivo transactivation of the pri-miR-202 promoter, demonstrating that pri-miR-202 may be a direct transcriptional target of SOX9/SF1 during testis differentiation. Our findings indicate that expression of the conserved gonad microRNA, miR-202-5p/3p, is downstream of the testis-determining factor SOX9, suggesting an early role in testis development.
authors.affiliation: Division of Molecular Genetics and Development, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Elanor N
authors.initials: EN
authors.lastname: Wainwright
authors.forename: Joan S
authors.initials: JS
authors.lastname: Jorgensen
authors.forename: Youngha
authors.initials: Y
authors.lastname: Kim
authors.forename: Vy
authors.initials: V
authors.lastname: Truong
authors.forename: Stefan
authors.initials: S
authors.lastname: Bagheri-Fam
authors.forename: Tara
authors.initials: T
authors.lastname: Davidson
authors.forename: Terje
authors.initials: T
authors.lastname: Svingen
authors.forename: Selene L
authors.initials: SL
authors.lastname: Fernandez-Valverde
authors.forename: Kathryn S
authors.initials: KS
authors.lastname: McClelland
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Taft
authors.forename: Vincent R
authors.initials: VR
authors.lastname: Harley
authors.forename: Peter
authors.initials: P
authors.lastname: Koopman
authors.forename: Dagmar
authors.initials: D
authors.lastname: Wilhelm
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D038081:Organogenesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D012708:Sertoli Cells / Q000166:cytology / Q000378:metabolism; D012733:Sex Differentiation / Q000235:genetics; D013737:Testis / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C583892:MIRN202 microRNA, mouse; D035683:MicroRNAs; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse
keywords: microRNAs; mouse gonad development; testis differentiation; transcriptional regulation; transgenic mice