Functions and Mechanisms of Action of the Medaka Sex-Determining Gene

• Project/Area Number: 14340259
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 生物形態・構造
• Research Institution: Okazaki National Research Institutes, National Institute for Basic Biology
• Principal Investigator: NAGAHAMA Yoshitaka National Institute for Basic Biology, Developmental Biology, Professor, 基礎生物学研究所, 教授 (50113428)
• Project Period (FY): 2002 – 2003
• Project Status: Completed (Fiscal Year 2003)
• Budget Amount: ¥14,100,000 (Direct Cost: ¥14,100,000); Fiscal Year 2003: ¥6,400,000 (Direct Cost: ¥6,400,000); Fiscal Year 2002: ¥7,700,000 (Direct Cost: ¥7,700,000)
• Keywords: Fish / Sex-determining gene / Testis / Sertoli cell / Sex differentiation / Medaka / DMY / DMRT1 / 性決定 / 精巣分化 / Y染色体 / 脊椎動物 / 特異抗体

Research Abstract

We previously identified PG17 as the leading candidate for the medaka sex-determining gene. To definitively identify PG17 as a sex-determining gene, we injected one-cell stage medaka embryos with a genomic DNA fragment carrying PG17. The transgenic embryos were bred until secondary sexual characters were observed. We found that all XX transgenic fish were male, showing that PG17 is sufficient to induce male development. The present data combined with our previous data indicate that PG17 is the sex-determining gene of medaka and named it DMY.
DMY mRNA and protein are expressed specifically in the somatic cells (Sertoli cells) surrounding primordial germ cells (PGC) in the early gonadal primordium, before morphological sex differences are apparent. DMRT1, another DM domain gene that is also involved in male development in other vertebrates, is expressed in spermatogonium-supporting cells after testicular differentiation (20-30 days after hatching). These results strongly suggest that DMY regulates PGC proliferation and differentiation sex-specifically during early gonadal differentiation of XY individuals and that DMRT1 regulates spermatogonial differentiation.
Because Sry transgenic mice are sterile and because DMY transgenic XX medakas are fertile, i.e., fully functional males, DMY transgenic medakas are the first transgenic vertebrates known to undergo complete sex reversal.

Research Products

• [Journal Article] Expression of aromatase mRNA and effects of aromatase inhibitor during ovarian development in the medaka, Oryzias latipes (2004)
  • Author(s): Suzuki, A. et al.
  • Journal Title: Journal of Experimental Zoology 301A Pages: 266-273
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Two DM domain genes, DMY and DMRT1, involved in testicular differentiation and development in the medaka, Oryzias latipes (2004)
  • Author(s): Kobayashi, T. et al.
  • Journal Title: Developmental Dynamics 231 Pages: 518-526
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Sexual plasticity in fish : A possible target of endocrine disruptor action (2004)
  • Author(s): Nagahama, Y. et al.
  • Journal Title: Environmental Sciences 11 Pages: 73-82
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Expression of aromatase mRNA and effects of aromatase inhibitor during ovarian development in the medaka, Oryzias latipes. (2004)
  • Author(s): Suzuki, A., Tanama, M., Nagahama, Y., Shibata, N.
  • Journal Title: J.Exp.Zool. 301A Pages: 266-273
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Two DM domain genes, DMY and DMRT1, involved in testicular differentiation and development in the medaka, Oryzias latipes. (2004)
  • Author(s): Kobayashi, T., Matsuda, M., Kajiura-Kobayashi, H., Suzuki, A., Saito, N., Nakamoto, M., Shibata, N., Nagahama, Y.
  • Journal Title: Dev.Dyn. 231 Pages: 518-526
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Sexual plasticity in fish : A possible target of endocrine disruptor actions. (2004)
  • Author(s): Nagahama, Y., Nakamura, M., Kitano, T., Tokumoto, T.
  • Journal Title: Environ.Sci. 11 Pages: 73-82
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Positional cloning of the sex-determining region of medaka using a Y congenic strain (2003)
  • Author(s): Matsuda, M. et al.
  • Journal Title: Aquatic Genomics Steps Toward a Great Future Pages: 236-243
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Expression of DMY and DMRT1 in various tissues of the medaka (Oryzias latipes) (2003)
  • Author(s): Ohmura-Matsuyama, Y. et al.
  • Journal Title: Zoological Science 20 Pages: 1395-4398
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Oryzias curvinotus has DMY, a gene that is required for male development in the medaka, O.latipes (2003)
  • Author(s): Matsuda, M. et al.
  • Journal Title: Zoological Science 20 Pages: 159-161
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Expression of DMY and DMRT1 in various tissues of the medaka (Oryzias latipes). (2003)
  • Author(s): Ohmuro-Matsuyama, Y., Matsuda, M., Kobayashi, T., Ikeuchi, T., Nagahama, Y.
  • Journal Title: Zool.Sci. 20 Pages: 1395-1398
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Oryzias curvinotus has DMY, a gene that is required for male development in the medaka (2003)
  • Author(s): Matsuda, M., Sato, T., Toyazaki, Y., Nagahama, Y., Hamaguchi, S., Sakaizumi, M.
  • Journal Title: O.latipes.Zool.Sci. 20 Pages: 159-161
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Sex determination and sex differentiation in fish : An overview of genetic, physiological, and environmental influences (2002)
  • Author(s): Devlin, R.H., Nagahama, Y.
  • Journal Title: Aquaculture 208 Pages: 191-366
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Sox9 in a teleost fish, medaka (Oryzias latipes) : Evidence for diversified function of Sox9 in gonad differentiation (2002)
  • Author(s): Yokoi, H. et al.
  • Journal Title: Molecular Reproduction and Development 63 Pages: 5-16
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] DMY is a Y-specific DM-domain gene required for male development in the medaka fish (2002)
  • Author(s): Matsuda, M. et al.
  • Journal Title: Nature 417 Pages: 559-563
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Sex determination and sex differentiation in fish (2002)
  • Author(s): Devlin, r.H., Nagahama, Y.
  • Journal Title: Aquaculture 208 Pages: 191-366
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Sox9 in a teleost fish, medaka (Oryzias latipes) : Evidence for diversified function of Sox9 in gonad differentiation. (2002)
  • Author(s): Yokoi, H., Kobayashi, T., Tanaka, M., Nagahama, Y., Wakamatsu, Y., Takeda, H., Araki, K., Morohashi, K., Ozato, K.
  • Journal Title: Mol.Reprod.Develop. 63 Pages: 5-16
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] DMY is a Y-specific DM-domain gene required for male development in the medaka fish. (2002)
  • Author(s): Matsuda, M., Nagahama, Y., Shinomiya, A., Sato, T., Matsuda, C., Kobayashi, T., Morrey, C.E., Shibata, N., Asakawa, S., Shimizu, N., Hori, H., Hamaguchi, S., Sakaizumi, M.
  • Journal Title: Nature 417 Pages: 559-563
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Positional cloning of the sex-determining region of medaka using a Y congenic strain. (2002)
  • Author(s): Matsuda, M., Nagahama, Y.
  • Journal Title: Aquatic Genomes : Steps Toward a Great Future.(N.Shimizu, T.Aoki, I.Hirono, F.Takashima (eds.)) Springer Pages: 236-243
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] M.Matsuda et al.: "DMY is a Y-specific DM-domain gene required for male development in the medaka fish"Nature. 417(6888). 559-563 (2002)
• [Publications] Y.Ohmuro-Matsuyama et al.: "Expression of DMY and DMRT1 in various tissues of the medaka (Oryzias latipes)"Zoological Science. 20. 1395-1398 (2003)
• [Publications] Y.Nagahama et al.: "Sexual plasticity in fish : A possible target of endocrine disruptor action"Environmental Sciences. 11(1). 73-82 (2004)
• [Publications] M.Matsuda Y.Nagahama: "Positional cloning of the sex-determining region of medaka using a Y congenic strain"Aquatic Genomics-Steps Toward a Great Future. 236-243 (2003)
• [Publications] 長濱嘉孝: "動物の性はどのように決まるか?-序論-"蛋白質 核酸 酵素. 49(2). 97-101 (2004)
• [Publications] 長濱嘉孝, 小林 亨, 松田 勝: "魚類の性決定と生殖腺の性分化/性転換"蛋白質 核酸 酵素. 49(2). 116-123 (2004)
• [Publications] M.Matsuda, Y.Nagahama et al.: "DMY is a Y-specific DM-domain gene required fro male development in the medaka"Nature. 417. 559-563 (2002)
• [Publications] M.Matsuda et al.: "oryzias curvinotus has DMY, a gene that is required for male development in the medaka, Oryzias latipes"Zoological Science. 20. 159-161 (2003)
• [Publications] R.H.Devlin, Y.Nagahama: "Sex determination and sex differentiation in fish"Aquaculture. 208. 191-366 (2002)