SOX9 regulates microRNA miR-202-5p/3p expression during mouse testis differentiation

Elanor N Wainwright; Joan S Jorgensen; Youngha Kim; Vy Truong; Stefan Bagheri-Fam; Tara Davidson; Terje Svingen; Selene L Fernandez-Valverde; Kathryn S McClelland; Ryan J Taft; Vincent R Harley; Peter Koopman; Dagmar Wilhelm

doi:10.1095/biolreprod.113.110155

SOX9 regulates microRNA miR-202-5p/3p expression during mouse testis differentiation

Authors:

Wainwright, Elanor N ;
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Jorgensen, Joan S ;
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Kim, Youngha ;
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Truong, Vy ;
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Bagheri-Fam, Stefan ;
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Davidson, Tara ;
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Svingen, Terje ;
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Department of Growth and Reproduction, Juliane Marie Centre, Rigshospitalet, The Capital Region of Denmark
Fernandez-Valverde, Selene L ;
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McClelland, Kathryn S ;
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Taft, Ryan J ;
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Harley, Vincent R ;
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Koopman, Peter ;
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Wilhelm, Dagmar
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DOI:

10.1095/biolreprod.113.110155

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.

Type:

Journal article

Language:

English

Published in:

Biology of Reproduction, 2013, Vol 89, Issue 2

Keywords:

Journal Article; Research Support, Non-U.S. Gov't; Animals; Cell Differentiation; Gene Expression Regulation, Developmental; Male; Mice; Mice, Knockout; MicroRNAs; Organogenesis; Promoter Regions, Genetic; SOX9 Transcription Factor; Sertoli Cells; Sex Differentiation; Testis; Transcription, Genetic

Main Research Area:

Medical science

Publication Status:

Published

Review type:

Peer Review

Submission year:

2013

Scientific Level:

Scientific

ID:

244378707

SOX9 regulates microRNA miR-202-5p/3p expression during mouse testis differentiation

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