Mechanisms of sex determination and gonadal sex differentiation in fish

• Project/Area Number: 16086213
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: National Institute for Basic Biology
• Principal Investigator: NAGAHAMA Yoshitaka National Institute for Basic Biology, 生殖生物学研究部門, 特任教授 (50113428)
• Project Period (FY): 2004 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥74,800,000 (Direct Cost: ¥74,800,000); Fiscal Year 2008: ¥4,400,000 (Direct Cost: ¥4,400,000); Fiscal Year 2007: ¥17,600,000 (Direct Cost: ¥17,600,000); Fiscal Year 2006: ¥17,600,000 (Direct Cost: ¥17,600,000); Fiscal Year 2005: ¥17,600,000 (Direct Cost: ¥17,600,000); Fiscal Year 2004: ¥17,600,000 (Direct Cost: ¥17,600,000)
• Keywords: 性決定 / 性分化 / 魚類 / 性決定遺伝子 / エストロゲン / DMRT1 / Foxl2 / 芳香化酵素 / メダカ / 生殖腺 / 性決定遺伝子DMY / Fox12 / ティラピア / 性決定遺伝子(DMY)

Research Abstract

本研究は、2種の雌雄異体魚(メダカとティラピア)を実験材料として、脊椎動物における性決定と生殖腺の性分化の分子メカニズムを解明することを目的として行った。その結果、DMYはメダカの雄への分化に必要かつ十分であること、魚類では、DMRT1は精巣の形成に不可欠であること、さらにFoxl2はcyp19a1(卵巣型芳香化酵素)遺伝子の発現促進を介して卵巣形成に重要な役割を果たすことが明らかとなった。

Research Products

• [Journal Article] Homology-modeled ligand-binding domains of medaka estrogen receptors and and rogen receptors : a model system for the study of reproduction (2009)
  • Author(s): Cui, J.Z., Shen, X. Y., Yan, Z.W., Zhao. H.B. and Nagahama. Y.
  • Journal Title: Biochem. Biophys. Res. Comm. 380 Pages: 115-121
  • Peer Reviewed
• [Journal Article] Stability in aromatase immunoreactivity of steroid-producing cells during early development of XX gonads of the Nile tilapia, Oreochromis niloticus : An organ culture study (2008)
  • Author(s): Sakai, F., Kobayashi, T., Matsuda, M. and Nagahama, Y
  • Journal Title: Zool. Sci 25 Pages: 344-348
  • NAID: 40016029309
  • Peer Reviewed
• [Journal Article] Sexual dimorphic expression of DMRT1 and Sox9 during gonadal differentiation and hormone-induced sex reversal in the teleost fish Nile tilapia (Oreochromis niloticus) (2008)
  • Author(s): Kobayashi, T., Kajiura-Kobayashi, H., Guan, G. and Nagahama, Y
  • Journal Title: Dev. Dyn 237 Pages: 297-306
  • Peer Reviewed
• [Journal Article] Sexual dimorphic expression of genes in gonads during early differentiation of a teleost fish, the Nile tilapia Oreochromis niloticus (2008)
  • Author(s): Ijiri, S., Kaneko, H., Kobayashi, T., Wang, D.S., Sakai, F., Paul-Prasanth, B., Nakamura M. and Nagahama, Y
  • Journal Title: Biol. Reprod 78 Pages: 333-341
  • Peer Reviewed
• [Journal Article] Stability in aromatase immunoreactivity of steroid-producing cells during early development of XX gonads of the Nile tilapia, Oreochromis niloticus : An organculture study (2008)
  • Author(s): Sakai, F., Kobayashi, T., Matsuda, M. and Nagahama, Y.
  • Journal Title: Zoological Science 25 Pages: 344-348
  • NAID: 40016029309
  • Peer Reviewed
• [Journal Article] Molecular cloning of Plkl and Nek2 and their expression in mature gonads of the teleost fish Nile tilapia (Oreochromis Niloticus) (2008)
  • Author(s): Matsuoka, Y., Kobayashi, T., Kihara, K. and Nagahama, Y.
  • Journal Title: Molecular Reproduction and Development 75 Pages: 989-1001
  • Peer Reviewed
• [Journal Article] Sexual dimorphic expression of genes in gonads during early differentiation of ateleost fish, the Nile tilapia Oreochromis niloticus. (2008)
  • Author(s): Ijiri, S., et. al.
  • Journal Title: Biology of Reproduction 78 Pages: 333-341
  • Peer Reviewed
• [Journal Article] Sexual dimorphic expression of DMRT1 and Sox9 during gonadal differentiation and hormone-induced sex reversal in the teleost fish Nile tilapia(Oreochromisniloticus) (2008)
  • Author(s): Kobayashi, T., et. al.
  • Journal Title: Developmental Dynamics 237 Pages: 297-306
  • Peer Reviewed
• [Journal Article] Characterization, expression and transcriptional regulation of P450c17-I and -II in the medaka, Oryzias latipes. Biochem (2007)
  • Author(s): Zhou, L.Y., Wang, D.S., Shibata, Y., Paul-Prasanth, B., Suzuki, A. and Nagahama, Y
  • Journal Title: Biophys. Res. Comm 362 Pages: 619-624
  • Peer Reviewed
• [Journal Article] A novel type of P450c17 lacking the lyase activity is responsible for C21-steroid biosynthesis in the fish ovary and head kidney (2007)
  • Author(s): Zhou, L.Y., Wang, D.S., Kobayashi, T., Yano, A., Paul-Prasanth, B., Suzuki, A., Sakai, F. and Nagahama, Y
  • Journal Title: Endocrinology 148 Pages: 4288-4291
  • Peer Reviewed
• [Journal Article] DMY gene induces male development in genetically female (XX) medaka fish. Proc. (2007)
  • Author(s): Matsuda, M., Shinomiya, S., Kinoshita, M., Suzuki, A., Kobayashi, T., Paul-Prasanth, B., Lau, E.L., Hamaguchi, S., Sakaizumi, M. and Nagahama, Y
  • Journal Title: Natl. Acad. Sci. USA 104 Pages: 3865-3870
  • Peer Reviewed
• [Journal Article] Foxl2 up-regulates aromatase gene transcription female-specifically by binding to the promoter as well as interacting with Ad4BP/SF-1 (2007)
  • Author(s): Wang, D.S., Kobayashi, T., Zhou, L.Y., Paul-Prasanth, B., Ijiri, S., Sakai, F., Okubo, K., Morohashi, K. and Nagahama, Y
  • Journal Title: Mol. Endocrinol 21 Pages: 712-725
  • Peer Reviewed
• [Journal Article] Molecular cloning of Dmrt1, Fox12 and Cyp19 in Southern catfish and their possible roles in sex differentiation. (2007)
  • Author(s): Liu, Z. H., et. al.
  • Journal Title: Journal of Endocrinology 194 Pages: 223-241
  • Peer Reviewed
• [Journal Article] Daxl suppresses P450arom expression in medaka ovarian follicles. (2007)
  • Author(s): Nakamoto, M., et. al.
  • Journal Title: Molecular Reproduction and Development 74 Pages: 1239-1246
  • Peer Reviewed
• [Journal Article] Characterization, expression and transcriptional regulation of P450c17-I and-II in the medaka, Oryzias latipes. (2007)
  • Author(s): Zhou, L. Y., et. al.
  • Journal Title: Biochemical and Biophysical Research Communication 362 Pages: 619-624
  • Peer Reviewed
• [Journal Article] A novel type of P450c17 lacking the lyase activity is responsible for C21-steroidbiosynthesis in the fish ovary and head kidney. (2007)
  • Author(s): Zhou, L. Y., et. al.
  • Journal Title: Endocrinology 148 Pages: 4288-4291
  • Peer Reviewed
• [Journal Article] Fox12 up-regulates aromatase gene transcription in a female-specific manner by binding to the promoter as well as interacting with Ad4BP/SF-1. (2007)
  • Author(s): Wang et al.
  • Journal Title: Molecular Endocrinology 21 Pages: 712-725
• [Journal Article] DMY gene induces male development in genetically female (XX) medaka fish. (2007)
  • Author(s): Matsuda, M. et al.
  • Journal Title: Proceedings of National Academy of Sciences, USA 104 Pages: 3865-3870
• [Journal Article] Knock-down of DMY initiates female pathway in the genetic male medaka, Oryzias latipes (2006)
  • Author(s): Paul-Prasanth, B., Matsuda, M., Lau, E.L., Suzuki, A., Sakai, F., Kobayashi, T. and Nagahama, Y
  • Journal Title: Biochem. Biophys. Res. Comm 351 Pages: 815-819
  • Peer Reviewed
• [Journal Article] Molecular cloning and analysis of gonadal expression of Fox12 in the medaka, Oryzias latipes. (2006)
  • Author(s): Nakamoto, M. et al.
  • Journal Title: Biochemical and Biophysical Research Communications 344 Pages: 2006-2006
• [Journal Article] Knock-down of DMY initiates female pathway in the genetic male medaka, Oryzias latipes. (2006)
  • Author(s): Paul-Prasanth, B. et al.
  • Journal Title: Biochemical and Biophysical Research Communication 351 Pages: 815-819
• [Journal Article] Forebrain gonadotropin-releasing hormone neuronal development : insights From transgenic medaka and the relevance to X-linked Kallmann syndrome (2006)
  • Author(s): Okubo, K.et al.
  • Journal Title: Endocrinology 147 Pages: 1076-1084
• [Journal Article] Suppression of steroidogenic enzyme expression during androgen-induced sex reversal in Nile tilapia (Oreochromis niloticus) (2006)
  • Author(s): Bhandari, RK.et al.
  • Journal Title: General and Comparative Endocrinology 145 Pages: 20-24
• [Journal Article] Liver receptor homologue-1 (lrh-1) activates the promoter of brain aromatase (cyp19a2) in a teleost fish, the medaka, Oryzias latipes (2006)
  • Author(s): Ohmuro-Matsuyama, Y.et al.
  • Journal Title: Molecular Reproduction and Development (In press)
• [Journal Article] Molecular mechanisms of sex differentiation and gonadal sex differentiation in fish (2006)
  • Author(s): Nagahama, Y.
  • Journal Title: Fish Physiology and Biochemistry (In press)
• [Journal Article] Ontogenic expression patterns of several nuclear receptors and cytochrome P450 aromatases in brain and gonads of the Nile tilapia Oreochromis niloticus suggests their involvement in sex differentiation (2006)
  • Author(s): Sudhakumari, C.C.et al.
  • Journal Title: Fish Physiology and Biochemistry (In press)
• [Journal Article] Molecular cloning, gene expression and characterization of the third estrogen receptor of the Nile tilapia, Oreochromis niloticus (2006)
  • Author(s): Wang, D.S.et al.
  • Journal Title: Fish Physiology and Biochemistry (In press)
• [Journal Article] Changes in steroidogenic enzyme and steroidogenic acute regulatory protein messenger RNAs in ovarian follicles during ovarian development of rainbow trout (Oncorhynchus mykiss) (2005)
  • Author(s): Nakamura, I., Evans, J.C., Kusakabe, M., Nagahama, Y. and Young, G.
  • Journal Title: Gen. Comp. Endocrinol 144 Pages: 224-231
  • Peer Reviewed
• [Journal Article] Cloning, expression and characterization of three types of 17β-hydroxysteroid dehydrogenases from the Nile tilapia, Oreochromis niloticus (2005)
  • Author(s): Zhou, L.Y., Wang, D.S., Senthilkumaran, S., Yoshikuni, M., Shibata, Y., Kobayashi, T., Sudhakumari, C.C. and Nagahama, Y
  • Journal Title: J. Mol. Endocrinol 35 Pages: 103-116
  • Peer Reviewed
• [Journal Article] Molecular cloning and expression of Ad4BP/SF-1 in the serial sex changing gobiid fish Trimma okinawae (2005)
  • Author(s): Kobayashi, Y.et al.
  • Journal Title: Biochemical and Biophysical Research Communications 332 Pages: 1073-1080
• [Journal Article] Aromatase immunoreactivity and the role of the enzymes in steroid pathways for inducing sex change in the hermaphrodite gobiid fish Trimma okinawae (2005)
  • Author(s): Sunobe, T.et al.
  • Journal Title: Comparative Biochemistry and Physiology, Part A 141 Pages: 54-59
• [Journal Article] Evidence that estrogen regulates the sex change of honeycomb grouper (Epinephelus merra), a protogynous hermaphrodite fish (2005)
  • Author(s): Bhandari, R.K.et al.
  • Journal Title: Journal of Experimental Zoology 303A Pages: 497-503
• [Journal Article] Two types of aromatase with different encoding genes, tissue distribution and developmental expression in Nile tilapia (2005)
  • Author(s): Chang, X.T.et al.
  • Journal Title: General and Comparative Endocrinology 141 Pages: 101-115
• [Journal Article] Cloning of cDNAs and the different expression of A-type cyclins and Dmc1 during spermatogenesis in the Japanese eel, a teleost fish (2005)
  • Author(s): Kobayashi-Kajiura, H.et al.
  • Journal Title: Developmental Dynamics 232 Pages: 1115-1123
• [Journal Article] Testicular type Sox9 is not involved in sex determination, but might be in the development of testicular structures in the medaka, Oryzias latipes (2005)
  • Author(s): Nakamoto, M.et al.
  • Journal Title: Biochemical and Biophysical Research Communications 333 Pages: 729-736
• [Journal Article] Changes in steroidogenic enzyme and steroidogenic acute regulatory protein messenger RNAs in ovarian follicles during ovarian development of rainbow trout (2005)
  • Author(s): Nakamura, I.et al.
  • Journal Title: General and Comparative Endocrinology 144 Pages: 224-231
• [Journal Article] Whole-cell electrophysiology of gonadotropin releasing hormone (GnRH) neurons that express green fluorescent protein (GFP) in the terminal nerve of transgenic medaka (Oryzias latipes) (2005)
  • Author(s): Wayne, N.I.et al.
  • Journal Title: Biology of Reproduction 73 Pages: 1228-1234
• [Journal Article] Cloning, expression and characterization of three types of 17β-hydroxysteroid dehydrogenases from the Nile tilapia, Oreochromis niloticus (2005)
  • Author(s): Zhou, L.Y.et al.
  • Journal Title: Journal of Molecular Endocrinology 35 Pages: 103-116
• [Journal Article] Gonadal structure of the serial-sex changing fish (2005)
  • Author(s): Kobayashi, Y.et al.
  • Journal Title: Development, Growth and Differentiation 47 Pages: 7-13
• [Journal Article] Molecular cloning and analysis of gonadal expression of Foxl2 in the medaka, Oryzias latipes (2005)
  • Author(s): Nakamoto, M.et al.
  • Journal Title: Biochemical and Biophysical Research Communications (In press)
• [Journal Article] Cloning, expression and characterization of three types of 17β-hydroxysteroid dehydrogeneases from the Nile tilapia, Oreochromis niloticus (2005)
  • Author(s): Zhou, L.Y.et al.
  • Journal Title: Journal of Molecular Endocrinology (In Press)
• [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
• [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
• [Journal Article] Molecular cloning and gene expression of Fox12 in the Nile tilapia, Oreochromis niloticus (2004)
  • Author(s): Wang, D.S.et al.
  • Journal Title: Biochemical and Biophysical Research Communications 320 Pages: 83-89
• [Presentation] Sex determination/differentiation and sexual plasticity in fish (2008)
  • Author(s): Nagahama, Y.
  • Organizer: XX Inter- national Congress of Zoology
  • Place of Presentation: Paris, France.
• [Presentation] Sex determination, differentiation and sexual plasticity in fish: Current status and future directions. (2008)
  • Author(s): Nagahama, Y.
  • Organizer: International Symposium on Sex Determination and Gametogenesis in Fish: Current Status and Future Directions
  • Place of Presentation: University of Hawaii, Honolulu, Hawaii, USA
• [Presentation] Organ culture and transplantation of tilapia(Oreochromis niloticus)gonads for the analysis of gonadal sex differentiation. (2007)
  • Author(s): Sakai, F., et. al.
  • Organizer: 6th Congress of the Asia and Oceania Society for comparative Endocrinology
  • Place of Presentation: Sliguri, West Bengal, India
  • Year and Date: 2007-12-11
• [Presentation] Molecular mechanisms of sex determination/differentiation in fish. (2007)
  • Author(s): 長濱嘉孝
  • Organizer: The International Symposium on Oryzias Fish
  • Place of Presentation: Bangkok, Thailand
  • Year and Date: 2007-11-12
• [Presentation] Functional analysis of the medaka sex determining gene, DMY reveals its role in the regulation of germ cell proliferation in the XY gonad. (2007)
  • Author(s): Paul-Prasanth, B., et. al.
  • Organizer: 8th International Symposium on Reproductive Physiology of Fish
  • Place of Presentation: Saint Malo, France
  • Year and Date: 2007-06-05
• [Presentation] Fox12 up-regulates aromatase gene transcription in a female-specific manner by binding to the promoter as well as interacting wiht Ad4BP/SF-1. (2007)
  • Author(s): Wang, D., et. al.
  • Organizer: 8th International Symposium on Reproductive Physiology of Fish
  • Place of Presentation: Saint Malo, France
  • Year and Date: 2007-06-05
• [Presentation] Hormonal regulation of oocyte maturation and ovulation in fish and starfish-comparative to general (2007)
  • Author(s): Nagahama, Y
  • Organizer: 6th Congress of the Asia and Oceania Society for Comparative Endocrinology (AOSCE)
  • Place of Presentation: Sliguri, Darjeeling, West Bengal, India
• [Presentation] Molecular mechanisms of sex determination/differentiation in fish (2007)
  • Author(s): Nagahama, Y.
  • Organizer: The International Symposium on Oryzias Fish
  • Place of Presentation: Bangkok, Thailand
• [Presentation] The second sex-determining gene in vertebrates (2005)
  • Author(s): Nagahama, Y. DMY
  • Organizer: 15th International Congress of Comparative Endocrinology.
  • Place of Presentation: Boston, USA
• [Book] 日本動物学会監修 (2007)
  • Author(s): 長濱嘉孝、井口泰泉共編
  • Total Pages: 256
  • Publisher: 内分泌と生命現象、シリーズ21世紀の動物科学
• [Book] 蛋白質核酸酵素(Vol. 49, 97-134) (2004)
  • Author(s): 長濱嘉孝
  • Publisher: 動物の性はそのように決まるか?
• [Remarks]
  • URL: http://www.nibb.ac.jp/seibunka/