SOX9 Regulates MicroRNA miR-202-5p/3p Expression During Mouse Testis Differentiation1
| Autor: | Dagmar Wilhelm, Elanor N. Wainwright, Joan S. Jorgensen, Kathryn S. McClelland, Tara Davidson, Peter Koopman, Selene L. Fernandez-Valverde, Vincent R. Harley, Youngha Kim, Stefan Bagheri-Fam, Ryan J. Taft, Terje Svingen, Vy Truong |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Regulation of gene expression
endocrine system Gonad Sexual differentiation urogenital system Cellular differentiation Male sex determination Cell Biology General Medicine SOX9 Biology Molecular biology medicine.anatomical_structure Testis determining factor Reproductive Medicine medicine Ectopic expression |
| Zdroj: | Biology of Reproduction. 89 |
| ISSN: | 1529-7268 0006-3363 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|