A microRNA (mmu-miR-124) prevents Sox9 expression in developing mouse ovarian cells.
In mammals, sex differentiation depends on gonad development, which is controlled by two groups of sex-determining genes that promote one gonadal sex and antagonize the opposite one. SOX9 plays a key role during testis development in all studied vertebrates, whereas it is kept inactive in the XX gonad at the critical time of sex determination, otherwise, ovary-to-testis gonadal sex reversal occurs. However, molecular mechanisms underlying repression of Sox9 at the beginning of ovarian development, as well as other important aspects of gonad organogenesis, remain largely unknown. Because there is indirect evidence that micro-RNAs (miRNA) are necessary for testicular function, the possible involvement of miRNAs in mammalian sex determination deserved further research. Using microarray technology, we have identified 22 miRNAs showing sex-specific expression in the developing gonads during the critical period of sex determination. Bioinformatics analyses led to the identification of miR-124 as the candidate gene for ovarian development. We knocked down or overexpressed miR-124 in primary gonadal cell cultures and observed that miR-124 is sufficient to induce the repression of both SOX9 translation and transcription in ovarian cells. Our results provide the first evidence of the involvement of a miRNA in the regulation of the gene controlling gonad development and sex determination. The miRNA microarray data reported here will help promote further research in this field, to unravel the role of other miRNAs in the genetic control of mammalian sex determination.
Departamento de Genética e Instituto de Biotecnología, Universidad de Granada, Centro de Investigación Biomédica, Granada, Spain.
Francisca M
FM
Real
Ryohei
R
Sekido
Darío G
DG
Lupiáñez
Robin
R
Lovell-Badge
Rafael
R
Jiménez
Miguel
M
Burgos
D000818:Animals; D021461:Animals, Outbred Strains; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D019295:Computational Biology; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D017930:Genes, Reporter; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D009866:Oogenesis; D010053:Ovary / Q000166:cytology / Q000378:metabolism*; D055758:SOX9 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012733:Sex Differentiation; D013737:Testis / Q000166:cytology / Q000378:metabolism
D035683:MicroRNAs; C540079:Mirn124 microRNA, mouse; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse
cell transfection; gene expression; gonad development; miR-124; microRNA; microarray; ovary; regulation of translation; sex determination