魚類における性決定と生殖腺の性分化の分子メカニズム

• 研究課題/領域番号: 16086213
• 研究種目: 特定領域研究
• 配分区分: 補助金
• 審査区分: 生物系
• 研究機関: 基礎生物学研究所
• 研究代表者: 長濱 嘉孝 基礎生物学研究所, 生殖生物学研究部門, 特任教授 (50113428)
• 研究期間 (年度): 2004 – 2008
• 研究課題ステータス: 完了 (2008年度)
• 配分額: 74,800千円 (直接経費: 74,800千円); 2008年度: 4,400千円 (直接経費: 4,400千円); 2007年度: 17,600千円 (直接経費: 17,600千円); 2006年度: 17,600千円 (直接経費: 17,600千円); 2005年度: 17,600千円 (直接経費: 17,600千円); 2004年度: 17,600千円 (直接経費: 17,600千円)
• キーワード: 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)

研究概要

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。

研究成果

• [雑誌論文] Homology-modeled ligand-binding domains of medaka estrogen receptors and and rogen receptors : a model system for the study of reproduction (2009)
  • 著者名/発表者名: Cui, J.Z., Shen, X. Y., Yan, Z.W., Zhao. H.B. and Nagahama. Y.
  • 雑誌名: Biochem. Biophys. Res. Comm. 380 ページ: 115-121
  • 査読あり
• [雑誌論文] 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)
  • 著者名/発表者名: Sakai, F., Kobayashi, T., Matsuda, M. and Nagahama, Y
  • 雑誌名: Zool. Sci 25 ページ: 344-348
  • NAID: 40016029309
  • 査読あり
• [雑誌論文] Sexual dimorphic expression of DMRT1 and Sox9 during gonadal differentiation and hormone-induced sex reversal in the teleost fish Nile tilapia (Oreochromis niloticus) (2008)
  • 著者名/発表者名: Kobayashi, T., Kajiura-Kobayashi, H., Guan, G. and Nagahama, Y
  • 雑誌名: Dev. Dyn 237 ページ: 297-306
  • 査読あり
• [雑誌論文] Sexual dimorphic expression of genes in gonads during early differentiation of a teleost fish, the Nile tilapia Oreochromis niloticus (2008)
  • 著者名/発表者名: Ijiri, S., Kaneko, H., Kobayashi, T., Wang, D.S., Sakai, F., Paul-Prasanth, B., Nakamura M. and Nagahama, Y
  • 雑誌名: Biol. Reprod 78 ページ: 333-341
  • 査読あり
• [雑誌論文] Stability in aromatase immunoreactivity of steroid-producing cells during early development of XX gonads of the Nile tilapia, Oreochromis niloticus : An organculture study (2008)
  • 著者名/発表者名: Sakai, F., Kobayashi, T., Matsuda, M. and Nagahama, Y.
  • 雑誌名: Zoological Science 25 ページ: 344-348
  • NAID: 40016029309
  • 査読あり
• [雑誌論文] Molecular cloning of Plkl and Nek2 and their expression in mature gonads of the teleost fish Nile tilapia (Oreochromis Niloticus) (2008)
  • 著者名/発表者名: Matsuoka, Y., Kobayashi, T., Kihara, K. and Nagahama, Y.
  • 雑誌名: Molecular Reproduction and Development 75 ページ: 989-1001
  • 査読あり
• [雑誌論文] Sexual dimorphic expression of genes in gonads during early differentiation of ateleost fish, the Nile tilapia Oreochromis niloticus. (2008)
  • 著者名/発表者名: Ijiri, S., et. al.
  • 雑誌名: Biology of Reproduction 78 ページ: 333-341
  • 査読あり
• [雑誌論文] Sexual dimorphic expression of DMRT1 and Sox9 during gonadal differentiation and hormone-induced sex reversal in the teleost fish Nile tilapia(Oreochromisniloticus) (2008)
  • 著者名/発表者名: Kobayashi, T., et. al.
  • 雑誌名: Developmental Dynamics 237 ページ: 297-306
  • 査読あり
• [雑誌論文] Characterization, expression and transcriptional regulation of P450c17-I and -II in the medaka, Oryzias latipes. Biochem (2007)
  • 著者名/発表者名: Zhou, L.Y., Wang, D.S., Shibata, Y., Paul-Prasanth, B., Suzuki, A. and Nagahama, Y
  • 雑誌名: Biophys. Res. Comm 362 ページ: 619-624
  • 査読あり
• [雑誌論文] A novel type of P450c17 lacking the lyase activity is responsible for C21-steroid biosynthesis in the fish ovary and head kidney (2007)
  • 著者名/発表者名: Zhou, L.Y., Wang, D.S., Kobayashi, T., Yano, A., Paul-Prasanth, B., Suzuki, A., Sakai, F. and Nagahama, Y
  • 雑誌名: Endocrinology 148 ページ: 4288-4291
  • 査読あり
• [雑誌論文] DMY gene induces male development in genetically female (XX) medaka fish. Proc. (2007)
  • 著者名/発表者名: Matsuda, M., Shinomiya, S., Kinoshita, M., Suzuki, A., Kobayashi, T., Paul-Prasanth, B., Lau, E.L., Hamaguchi, S., Sakaizumi, M. and Nagahama, Y
  • 雑誌名: Natl. Acad. Sci. USA 104 ページ: 3865-3870
  • 査読あり
• [雑誌論文] Foxl2 up-regulates aromatase gene transcription female-specifically by binding to the promoter as well as interacting with Ad4BP/SF-1 (2007)
  • 著者名/発表者名: Wang, D.S., Kobayashi, T., Zhou, L.Y., Paul-Prasanth, B., Ijiri, S., Sakai, F., Okubo, K., Morohashi, K. and Nagahama, Y
  • 雑誌名: Mol. Endocrinol 21 ページ: 712-725
  • 査読あり
• [雑誌論文] Molecular cloning of Dmrt1, Fox12 and Cyp19 in Southern catfish and their possible roles in sex differentiation. (2007)
  • 著者名/発表者名: Liu, Z. H., et. al.
  • 雑誌名: Journal of Endocrinology 194 ページ: 223-241
  • 査読あり
• [雑誌論文] Daxl suppresses P450arom expression in medaka ovarian follicles. (2007)
  • 著者名/発表者名: Nakamoto, M., et. al.
  • 雑誌名: Molecular Reproduction and Development 74 ページ: 1239-1246
  • 査読あり
• [雑誌論文] Characterization, expression and transcriptional regulation of P450c17-I and-II in the medaka, Oryzias latipes. (2007)
  • 著者名/発表者名: Zhou, L. Y., et. al.
  • 雑誌名: Biochemical and Biophysical Research Communication 362 ページ: 619-624
  • 査読あり
• [雑誌論文] A novel type of P450c17 lacking the lyase activity is responsible for C21-steroidbiosynthesis in the fish ovary and head kidney. (2007)
  • 著者名/発表者名: Zhou, L. Y., et. al.
  • 雑誌名: Endocrinology 148 ページ: 4288-4291
  • 査読あり
• [雑誌論文] 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)
  • 著者名/発表者名: Wang et al.
  • 雑誌名: Molecular Endocrinology 21 ページ: 712-725
• [雑誌論文] DMY gene induces male development in genetically female (XX) medaka fish. (2007)
  • 著者名/発表者名: Matsuda, M. et al.
  • 雑誌名: Proceedings of National Academy of Sciences, USA 104 ページ: 3865-3870
• [雑誌論文] Knock-down of DMY initiates female pathway in the genetic male medaka, Oryzias latipes (2006)
  • 著者名/発表者名: Paul-Prasanth, B., Matsuda, M., Lau, E.L., Suzuki, A., Sakai, F., Kobayashi, T. and Nagahama, Y
  • 雑誌名: Biochem. Biophys. Res. Comm 351 ページ: 815-819
  • 査読あり
• [雑誌論文] Molecular cloning and analysis of gonadal expression of Fox12 in the medaka, Oryzias latipes. (2006)
  • 著者名/発表者名: Nakamoto, M. et al.
  • 雑誌名: Biochemical and Biophysical Research Communications 344 ページ: 2006-2006
• [雑誌論文] Knock-down of DMY initiates female pathway in the genetic male medaka, Oryzias latipes. (2006)
  • 著者名/発表者名: Paul-Prasanth, B. et al.
  • 雑誌名: Biochemical and Biophysical Research Communication 351 ページ: 815-819
• [雑誌論文] Forebrain gonadotropin-releasing hormone neuronal development : insights From transgenic medaka and the relevance to X-linked Kallmann syndrome (2006)
  • 著者名/発表者名: Okubo, K.et al.
  • 雑誌名: Endocrinology 147 ページ: 1076-1084
• [雑誌論文] Suppression of steroidogenic enzyme expression during androgen-induced sex reversal in Nile tilapia (Oreochromis niloticus) (2006)
  • 著者名/発表者名: Bhandari, RK.et al.
  • 雑誌名: General and Comparative Endocrinology 145 ページ: 20-24
• [雑誌論文] Liver receptor homologue-1 (lrh-1) activates the promoter of brain aromatase (cyp19a2) in a teleost fish, the medaka, Oryzias latipes (2006)
  • 著者名/発表者名: Ohmuro-Matsuyama, Y.et al.
  • 雑誌名: Molecular Reproduction and Development (In press)
• [雑誌論文] Molecular mechanisms of sex differentiation and gonadal sex differentiation in fish (2006)
  • 著者名/発表者名: Nagahama, Y.
  • 雑誌名: Fish Physiology and Biochemistry (In press)
• [雑誌論文] 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)
  • 著者名/発表者名: Sudhakumari, C.C.et al.
  • 雑誌名: Fish Physiology and Biochemistry (In press)
• [雑誌論文] Molecular cloning, gene expression and characterization of the third estrogen receptor of the Nile tilapia, Oreochromis niloticus (2006)
  • 著者名/発表者名: Wang, D.S.et al.
  • 雑誌名: Fish Physiology and Biochemistry (In press)
• [雑誌論文] Changes in steroidogenic enzyme and steroidogenic acute regulatory protein messenger RNAs in ovarian follicles during ovarian development of rainbow trout (Oncorhynchus mykiss) (2005)
  • 著者名/発表者名: Nakamura, I., Evans, J.C., Kusakabe, M., Nagahama, Y. and Young, G.
  • 雑誌名: Gen. Comp. Endocrinol 144 ページ: 224-231
  • 査読あり
• [雑誌論文] Cloning, expression and characterization of three types of 17β-hydroxysteroid dehydrogenases from the Nile tilapia, Oreochromis niloticus (2005)
  • 著者名/発表者名: Zhou, L.Y., Wang, D.S., Senthilkumaran, S., Yoshikuni, M., Shibata, Y., Kobayashi, T., Sudhakumari, C.C. and Nagahama, Y
  • 雑誌名: J. Mol. Endocrinol 35 ページ: 103-116
  • 査読あり
• [雑誌論文] Molecular cloning and expression of Ad4BP/SF-1 in the serial sex changing gobiid fish Trimma okinawae (2005)
  • 著者名/発表者名: Kobayashi, Y.et al.
  • 雑誌名: Biochemical and Biophysical Research Communications 332 ページ: 1073-1080
• [雑誌論文] Aromatase immunoreactivity and the role of the enzymes in steroid pathways for inducing sex change in the hermaphrodite gobiid fish Trimma okinawae (2005)
  • 著者名/発表者名: Sunobe, T.et al.
  • 雑誌名: Comparative Biochemistry and Physiology, Part A 141 ページ: 54-59
• [雑誌論文] Evidence that estrogen regulates the sex change of honeycomb grouper (Epinephelus merra), a protogynous hermaphrodite fish (2005)
  • 著者名/発表者名: Bhandari, R.K.et al.
  • 雑誌名: Journal of Experimental Zoology 303A ページ: 497-503
• [雑誌論文] Two types of aromatase with different encoding genes, tissue distribution and developmental expression in Nile tilapia (2005)
  • 著者名/発表者名: Chang, X.T.et al.
  • 雑誌名: General and Comparative Endocrinology 141 ページ: 101-115
• [雑誌論文] Cloning of cDNAs and the different expression of A-type cyclins and Dmc1 during spermatogenesis in the Japanese eel, a teleost fish (2005)
  • 著者名/発表者名: Kobayashi-Kajiura, H.et al.
  • 雑誌名: Developmental Dynamics 232 ページ: 1115-1123
• [雑誌論文] Testicular type Sox9 is not involved in sex determination, but might be in the development of testicular structures in the medaka, Oryzias latipes (2005)
  • 著者名/発表者名: Nakamoto, M.et al.
  • 雑誌名: Biochemical and Biophysical Research Communications 333 ページ: 729-736
• [雑誌論文] Changes in steroidogenic enzyme and steroidogenic acute regulatory protein messenger RNAs in ovarian follicles during ovarian development of rainbow trout (2005)
  • 著者名/発表者名: Nakamura, I.et al.
  • 雑誌名: General and Comparative Endocrinology 144 ページ: 224-231
• [雑誌論文] 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)
  • 著者名/発表者名: Wayne, N.I.et al.
  • 雑誌名: Biology of Reproduction 73 ページ: 1228-1234
• [雑誌論文] Cloning, expression and characterization of three types of 17β-hydroxysteroid dehydrogenases from the Nile tilapia, Oreochromis niloticus (2005)
  • 著者名/発表者名: Zhou, L.Y.et al.
  • 雑誌名: Journal of Molecular Endocrinology 35 ページ: 103-116
• [雑誌論文] Gonadal structure of the serial-sex changing fish (2005)
  • 著者名/発表者名: Kobayashi, Y.et al.
  • 雑誌名: Development, Growth and Differentiation 47 ページ: 7-13
• [雑誌論文] Molecular cloning and analysis of gonadal expression of Foxl2 in the medaka, Oryzias latipes (2005)
  • 著者名/発表者名: Nakamoto, M.et al.
  • 雑誌名: Biochemical and Biophysical Research Communications (In press)
• [雑誌論文] Cloning, expression and characterization of three types of 17β-hydroxysteroid dehydrogeneases from the Nile tilapia, Oreochromis niloticus (2005)
  • 著者名/発表者名: Zhou, L.Y.et al.
  • 雑誌名: Journal of Molecular Endocrinology (In Press)
• [雑誌論文] Two DM domain genes, DMY and DMRT1, involved in testicular Differentiation and development in the medaka, Oryzias latipes (2004)
  • 著者名/発表者名: Kobayashi, T. et al.
  • 雑誌名: Developmental Dynamics 231 ページ: 518-526
• [雑誌論文] Expression of aromatase mRNA and effects of aromatase inhibitor during ovarian development in the medaka, Oryzias latipes (2004)
  • 著者名/発表者名: Suzuki, A. et al.
  • 雑誌名: Journal of Experimental Zoology 301A ページ: 266-273
• [雑誌論文] Molecular cloning and gene expression of Fox12 in the Nile tilapia, Oreochromis niloticus (2004)
  • 著者名/発表者名: Wang, D.S.et al.
  • 雑誌名: Biochemical and Biophysical Research Communications 320 ページ: 83-89
• [学会発表] Sex determination/differentiation and sexual plasticity in fish (2008)
  • 著者名/発表者名: Nagahama, Y.
  • 学会等名: XX Inter- national Congress of Zoology
  • 発表場所: Paris, France.
• [学会発表] Sex determination, differentiation and sexual plasticity in fish: Current status and future directions. (2008)
  • 著者名/発表者名: Nagahama, Y.
  • 学会等名: International Symposium on Sex Determination and Gametogenesis in Fish: Current Status and Future Directions
  • 発表場所: University of Hawaii, Honolulu, Hawaii, USA
• [学会発表] Organ culture and transplantation of tilapia(Oreochromis niloticus)gonads for the analysis of gonadal sex differentiation. (2007)
  • 著者名/発表者名: Sakai, F., et. al.
  • 学会等名: 6th Congress of the Asia and Oceania Society for comparative Endocrinology
  • 発表場所: Sliguri, West Bengal, India
  • 年月日: 2007-12-11
• [学会発表] Molecular mechanisms of sex determination/differentiation in fish. (2007)
  • 著者名/発表者名: 長濱嘉孝
  • 学会等名: The International Symposium on Oryzias Fish
  • 発表場所: Bangkok, Thailand
  • 年月日: 2007-11-12
• [学会発表] Functional analysis of the medaka sex determining gene, DMY reveals its role in the regulation of germ cell proliferation in the XY gonad. (2007)
  • 著者名/発表者名: Paul-Prasanth, B., et. al.
  • 学会等名: 8th International Symposium on Reproductive Physiology of Fish
  • 発表場所: Saint Malo, France
  • 年月日: 2007-06-05
• [学会発表] 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)
  • 著者名/発表者名: Wang, D., et. al.
  • 学会等名: 8th International Symposium on Reproductive Physiology of Fish
  • 発表場所: Saint Malo, France
  • 年月日: 2007-06-05
• [学会発表] Hormonal regulation of oocyte maturation and ovulation in fish and starfish-comparative to general (2007)
  • 著者名/発表者名: Nagahama, Y
  • 学会等名: 6th Congress of the Asia and Oceania Society for Comparative Endocrinology (AOSCE)
  • 発表場所: Sliguri, Darjeeling, West Bengal, India
• [学会発表] Molecular mechanisms of sex determination/differentiation in fish (2007)
  • 著者名/発表者名: Nagahama, Y.
  • 学会等名: The International Symposium on Oryzias Fish
  • 発表場所: Bangkok, Thailand
• [学会発表] The second sex-determining gene in vertebrates (2005)
  • 著者名/発表者名: Nagahama, Y. DMY
  • 学会等名: 15th International Congress of Comparative Endocrinology.
  • 発表場所: Boston, USA
• [図書] 日本動物学会監修 (2007)
  • 著者名/発表者名: 長濱嘉孝、井口泰泉共編
  • 総ページ数: 256
  • 出版者: 内分泌と生命現象、シリーズ21世紀の動物科学
• [図書] 蛋白質核酸酵素(Vol. 49, 97-134) (2004)
  • 著者名/発表者名: 長濱嘉孝
  • 出版者: 動物の性はそのように決まるか?
• [備考]
  • URL: http://www.nibb.ac.jp/seibunka/