TY - JOUR
T1 - Rspo1-activated signalling molecules are sufficient to induce ovarian differentiation in XY medaka (Oryzias latipes)
AU - Zhou, Linyan
AU - Charkraborty, Tapas
AU - Zhou, Qian
AU - Mohapatra, Sipra
AU - Nagahama, Yoshitaka
AU - Zhang, Yueguang
N1 - Funding Information:
This work was supported by grants from the National Natural Science Foundation of China (31201986), Science and Technology Agency (SORST Program), the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan, Research Foundation of Talent Introduction of Southwest University, China (SWU111003), a grant from Natural Science Foundation Project of CQ CSTC, China (cstc2012jjA80005), and the special fund of Chongqing key laboratory (CSTC). The authors are thankful to National BioResource Project (NBRP) for providing the medaka strains.
PY - 2016/1/19
Y1 - 2016/1/19
N2 - 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.
AB - 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.
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U2 - 10.1038/srep19543
DO - 10.1038/srep19543
M3 - Article
C2 - 26782368
AN - SCOPUS:84955608970
SN - 2045-2322
VL - 6
JO - Scientific reports
JF - Scientific reports
M1 - 19543
ER -