TY - JOUR
T1 - Dmy initiates masculinity by altering Gsdf/Sox9a2/Rspo1 expression in medaka (Oryzias latipes)
AU - Chakraborty, Tapas
AU - Zhou, Lin Yan
AU - Chaudhari, Aparna
AU - Iguchi, Taisen
AU - Nagahama, Y.
N1 - Funding Information:
We thank Dr. M. Matsuda (Utsunomiya University, Japan), Dr. Y. Ogino (National Institute for Basic Biology, Japan) and Dr. P. Krisnan (ICAR, India) for their help. We extend our gratitude to Dr. Hiroshi Mitani for providing different medaka cell lines. QurtE and olvas-eGFP transgenic strain of medaka was provided by National Bio Resource Project Medaka (NBRP Medaka) of Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan. This work was in part supported by Grants from Science and Technology Agency (SORST Program) and the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan.
PY - 2016/1/25
Y1 - 2016/1/25
N2 - 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.
AB - 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.
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U2 - 10.1038/srep19480
DO - 10.1038/srep19480
M3 - Article
C2 - 26806354
AN - SCOPUS:84955494990
SN - 2045-2322
VL - 6
JO - Scientific Reports
JF - Scientific Reports
M1 - 19480
ER -