SOX9 Regulates MicroRNA miR-202-5p/3p expression during mouse testis differentiation

Wainwright, Elanor N., Jorgensen, Joan S., Kim, Youngha, Truong, Vy, Bagheri-Fam, Stefan, Davidson, Tara, Svingen, Terje, Fernandez-Valverde, Selene L., McClelland, Kathryn S., Taft, Ryan J., Harley, Vincent R., Koopman, Peter and Wilhelm, Dagmar (2013) SOX9 Regulates MicroRNA miR-202-5p/3p expression during mouse testis differentiation. Biology of Reproduction, 89 2: . doi:10.1095/biolreprod.113.110155


Author Wainwright, Elanor N.
Jorgensen, Joan S.
Kim, Youngha
Truong, Vy
Bagheri-Fam, Stefan
Davidson, Tara
Svingen, Terje
Fernandez-Valverde, Selene L.
McClelland, Kathryn S.
Taft, Ryan J.
Harley, Vincent R.
Koopman, Peter
Wilhelm, Dagmar
Title SOX9 Regulates MicroRNA miR-202-5p/3p expression during mouse testis differentiation
Journal name Biology of Reproduction   Check publisher's open access policy
ISSN 0006-3363
1529-7268
Publication date 2013-08-01
Year available 2013
Sub-type Article (original research)
DOI 10.1095/biolreprod.113.110155
Open Access Status DOI
Volume 89
Issue 2
Total pages 12
Place of publication Madison, WI United States
Publisher Society for the Study of Reproduction
Language eng
Subject 1307 Cell Biology
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.
Formatted 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.
Keyword MicroRNAs
Mouse gonad development
Testis Differentiation
Transcriptional Regulation
Transgenic mice
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID DP0879913
631460
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
 
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