title: Dmy initiates masculinity by altering Gsdf/Sox9a2/Rspo1 expression in medaka (Oryzias latipes).
abstract: Despite identification of several sex-determining genes in non-mammalian vertebrates, their detailed molecular cascades of sex determination/differentiation are not known. Here, we used a novel RNAi to characterise the molecular mechanism of Dmy (the sex-determining gene of medaka)-mediated masculinity in XY fish. Dmy knockdown (Dmy-KD) suppressed male pathway (Gsdf, Sox9a2, etc.) and favoured female cascade (Rspo1, etc.) in embryonic XY gonads, resulting in a fertile male-to-female sex-reversal. Gsdf, Sox9a2, and Rspo1 directly interacted with Dmy, and co-injection of Gsdf and Sox9a2 re-established masculinity in XY-Dmy-KD transgenics, insinuating that Dmy initiates masculinity by stimulating and suppressing Gsdf/Sox9a2 and Rspo1 expression, respectively. Gonadal expression of Wt1a starts prior to Dmy and didn't change upon Dmy-KD. Furthermore, Wt1a stimulated the promoter activity of Dmy, suggesting Wt1a as a regulator of Dmy. These findings provide new insights into the role of vertebrate sex-determining genes associated with the molecular interplay between the male and female pathways.
authors.affiliation: Laboratory of Reproductive Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan.|SORST, Japan Science Technology Corporation, Kawaguchi, Saitama 332-0012, Japan.|South Ehime Fisheries Research Center, Institution for Collaborative Relations, Ehime University, Nishiura, 798-4206, Japan.|Key Laboratory of Aquatic Science of Chongqing, School of Life Science, Southwest University, Chongqing, 400715, China.|South Ehime Fisheries Research Center, Institution for Collaborative Relations, Ehime University, Matsuyama 790-8577, Japan.
authors.forename: Tapas
authors.initials: T
authors.lastname: Chakraborty
authors.affiliation: Laboratory of Reproductive Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan.|SORST, Japan Science Technology Corporation, Kawaguchi, Saitama 332-0012, Japan.|Key Laboratory of Aquatic Science of Chongqing, School of Life Science, Southwest University, Chongqing, 400715, China.
authors.forename: Lin Yan
authors.initials: LY
authors.lastname: Zhou
authors.affiliation: Central Institute of Fisheries Education, Mumbai, 400061, India.
authors.forename: Aparna
authors.initials: A
authors.lastname: Chaudhari
authors.affiliation: Laboratory of Molecular Environmental Endocrinology, Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, Okazaki 444-8787, Japan.
authors.forename: Taisen
authors.initials: T
authors.lastname: Iguchi
authors.affiliation: Laboratory of Reproductive Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan.|SORST, Japan Science Technology Corporation, Kawaguchi, Saitama 332-0012, Japan.|South Ehime Fisheries Research Center, Institution for Collaborative Relations, Ehime University, Matsuyama 790-8577, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nagahama
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D005260:Female; D029941:Fish Proteins / Q000096:biosynthesis / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006066:Gonads / Q000254:growth & development; D008297:Male; D009154:Mutation; D009990:Oryzias / Q000235:genetics* / Q000254:growth & development; D055758:SOX9 Transcription Factor / Q000235:genetics; D019849:Sex Determination Processes / Q000235:genetics*; D019699:Thrombospondins / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D025721:WT1 Proteins / Q000235:genetics; D014998:Y Chromosome / Q000235:genetics
chemical_list: D029941:Fish Proteins; D055758:SOX9 Transcription Factor; D019699:Thrombospondins; D016212:Transforming Growth Factor beta; D025721:WT1 Proteins