title: Rspo1-activated signalling molecules are sufficient to induce ovarian differentiation in XY medaka (Oryzias latipes).
abstract: In contrast to our understanding of testicular differentiation, ovarian differentiation is less well understood in vertebrates. In mammals, R-spondin1 (Rspo1), an activator of Wnt/β-catenin signaling pathway, is located upstream of the female sex determination pathway. However, the functions of Rspo1 in ovarian differentiation remain unclear in non-mammalian species. In order to elucidate the detailed functions of Rspo/Wnt signaling pathway in fish sex determination/differentiation, the ectopic expression of the Rspo1 gene was performed in XY medaka (Oryzias latipes). The results obtained demonstrated that the gain of Rspo1 function induced femininity in XY fish. The overexpression of Rspo1 enhanced Wnt4b and β-catenin transcription, and completely suppressed the expression of male-biased genes (Dmy, Gsdf, Sox9a2 and Dmrt1) as well as testicular differentiation. Gonadal reprograming of Rspo1-over-expressed-XY (Rspo1-OV-XY) fish, induced the production of female-biased genes (Cyp19a1a and Foxl2), estradiol-17β production and further female type secondary sexuality. Moreover, Rspo1-OV-XY females were fertile and produced successive generations. Promoter analyses showed that Rspo1 transcription was directly regulated by DM domain genes (Dmy, the sex-determining gene, and Dmrt1) and remained unresponsive to Foxl2. Taken together, our results strongly suggest that Rspo1 is sufficient to activate ovarian development and plays a decisive role in the ovarian differentiation in medaka.
authors.affiliation: Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Science, Southwest University, Chongqing 400715, P.R. China.|SORST, Japan Science Technology Corporation, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Linyan
authors.initials: L
authors.lastname: Zhou
authors.affiliation: SORST, Japan Science Technology Corporation, Kawaguchi, Saitama 332-0012, Japan.|South Ehime Fisheries Research Center, Ehime University, Ainan, Ehime, 798-4206, Japan.
authors.forename: Tapas
authors.initials: T
authors.lastname: Charkraborty
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 305-8577, Ibaraki, Japan.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: South Ehime Fisheries Research Center, Ehime University, Ainan, Ehime, 798-4206, Japan.
authors.forename: Sipra
authors.initials: S
authors.lastname: Mohapatra
authors.affiliation: SORST, Japan Science Technology Corporation, Kawaguchi, Saitama 332-0012, Japan.|South Ehime Fisheries Research Center, Ehime University, Ainan, Ehime, 798-4206, Japan.|Institution for Collaborative Relations, Ehime University, 790-8577, Matsuyama, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Nagahama
authors.affiliation: Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Science, Southwest University, Chongqing 400715, P.R. China.
authors.forename: Yueguang
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D005260:Female; D029941:Fish Proteins / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D008297:Male; D009990:Oryzias / Q000235:genetics* / Q000254:growth & development* / Q000502:physiology; D010053:Ovary / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D019849:Sex Determination Processes / Q000235:genetics / Q000502:physiology; D012733:Sex Differentiation / Q000235:genetics* / Q000502:physiology; D013737:Testis / Q000502:physiology; D014158:Transcription, Genetic / Q000235:genetics; D060528:Wnt4 Protein / Q000235:genetics; D051176:beta Catenin / Q000235:genetics
chemical_list: D029941:Fish Proteins; D060528:Wnt4 Protein; D051176:beta Catenin