2008 Fiscal Year Final Research Report
A spatiotemporal SRY action in mammalian gonadal sex determination
Project/Area Number |
16086203
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Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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Allocation Type | Single-year Grants |
Review Section |
Biological Sciences
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Research Institution | The University of Tokyo |
Principal Investigator |
KANAI Yoshiakira The University of Tokyo, 大学院・農学生命科学研究科, 准教授 (30260326)
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Co-Investigator(Kenkyū-buntansha) |
TSUNEKAWA NAOKI 東京大学, 大学院・農学生命科学研究科, 助教 (50431838)
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Project Period (FY) |
2004 – 2008
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Keywords | SRY / トランスジェニック / 性決定 / マウス |
Research Abstract |
本研究課題により、新たにSry機能解析用のモデル動物の樹立を目的とし、マウスHsp70プロモーターにSryを連結した発現ベクターを用いて、Sry発現様式を改変したトランスジェニック(Tg)マウスの樹立を行った。その結果、ステージ・領域非特異的かつ恒常的にSry発現するXX精巣の性転換ライン(#40、#46)2系統を樹立した。さらに、通常飼育下で繁殖能があり(XX卵巣)、人為的に熱ショック(HS)を与えることにより、卵巣からXX精巣へと性転換させることができるSry誘導モデルマウス(#44)の樹立に初めて成功した。本モデルマウスを用いて、1)性分化初期(11.0~11.25dpc)でのSry発現が精巣誘導に必須であること(精巣誘導の臨界期の決定)、2)初期のSry発現がWnt4の発現の抑制に必須であること、3)SRYのみならずFGF9因子が時空間的なSox9発現制御に重要であること、4)Sry直下のカスケードに雄特異的に性腺にエネルギー供給する分子メカニズムの存在、5)Sry単独では完全な精子形成能を持つセルトリ細胞に分化できないこと(XX/Sryセルトリ細胞の機能不全)、6)Sry誘導により6時間以内に発現誘導されるSRY標的遺伝子を新たに78個の遺伝子を同定-などを見い出した。
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[Journal Article] A critical time windows of Sry action in gonadal sex differentiation in mice2009
Author(s)
Hiramatsu, R., Matoba, S., Kanai-Azuma, M., Tsunekawa, N., Katoh-Fukui, Y., Kurohmaru, M., Morohashi, K., Wilhelm, D., Koopman, P., Kanai, Y
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Journal Title
Development 36(1)
Pages: 129-138
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[Journal Article] The Cerebellin 4 Precursor Gene Is a Direct Target of SRY and SOX9 in Mice2009
Author(s)
Bradford, S.T., Hiramatsu, R., Maddugoda, M.P., Bernard, P., Chaboissier, M.C., Sinclair, A., Schedl, A., Harley, V., Kanai, Y., Koopman, P., Wilhelm, D
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Journal Title
Biol. Reprod 80(6)
Pages: 1178-1188
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[Journal Article] Five azacytidine, a DNA methyltranseferase inhibitor, specifically inhibits the testicualar cord formation and Sertoli cell differentiation, in vitro2008
Author(s)
Mizukami, T., Kanai, Y., Fujisawa, M., Kanai-Azuma, M., Kurohmaru, M., Hayashi, Y
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Journal Title
Mol. Reprod. Dev 75(6)
Pages: 1002-1010
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[Journal Article] Akt signaling promotes derivation of embryonic germ cells from primordial germ cells2008
Author(s)
Kimura, T., Tomooka, M., Yamano, N., Murayama, K., Matoba, S., Umehara, H., Kanai, Y., Nakano, T
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Journal Title
Development 135(5)
Pages: 869-879
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[Journal Article] Establishment of testis-specific SOX9 activation requires high-glucose metabolism in mouse sex differentiation2008
Author(s)
Matoba, S., Hiramatsu, R., Kanai-Azuma, M., Tsunekawa, N., Harikae, K., Kawakami, H., Kurohmaru, M., Kanai, Y
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Journal Title
Dev Biol 324(1)
Pages: 76-87
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[Journal Article] Potency of testicular somatic environment to support spermatogenesis in XX/Sry transgenic male mice2007
Author(s)
Ishii, M., Tachiwana, T., Hoshino, A., Tsunekawa, N., Hiramatsu, R., Matoba, S., Kanai-Azuma, M., Kawakami H., Kurohmaru, M., Kanai, Y
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Journal Title
Development 134
Pages: 449-454
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[Journal Article] SOX9 regulates prostaglandin D synthase gene transcription in vivo to ensure testis development2007
Author(s)
Wilhelm, D., Hiramatsu, R., Mizusaki, H., Widjaja, L., Combes, A.N., Kanai, Y., Koopman, P
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Journal Title
J. Biol. Chem 282
Pages: 10553-10560
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[Journal Article] Redundant roles of Sox17 and Sox18 in early cardiovascular development of mouse embryos. Biochem. Biophys2007
Author(s)
Sakamoto, Y., Hara, K., Kanai-Azuma, M., Matsui, T., Miura, Y., Tsunekawa, N., Kurohmaru, M., Saijoh, Y., Koopman, P., Kanai, Y
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Journal Title
Res. Commun 360(3)
Pages: 539-544
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[Journal Article] Isolation, characterization, and in vitro and in vivo differentiation of putative thecal stem cells. Proc. Natl2007
Author(s)
Honda, A., Hirose, M., Hara, K., Matoba, S., Inoue, K., Hiura, H., Miki, H., Kanai, Y., Kono, T., Shinohara, T., Ogura A
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Journal Title
Acad. Sci. USA 104(30)
Pages: 12389-12394
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[Journal Article] Sox17 plays a substantial role in late-stage differentiation of the extraembryonic endoderm in vitro2007
Author(s)
Shimoda, M, Kanai-Azuma, M., Hara, K., Miyazaki, S., Kanai, Y., Monden, M., Miyazaki, J
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Journal Title
J. Cell Sci 120(21)
Pages: 3859-3869
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[Journal Article] Crucial transcription factors in endoderm and embryonic gut development are expressed in gut-like structures from mouse ES cells2006
Author(s)
Matsuura, R., Kogo, H., Ogaeri, T., Miwa, T., Kuwahara, M., Kanai, Y., Nakagawa, T., Kuroiwa, A., Fujimoto, T., Torihashi, S
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Journal Title
Stem Cells 24(3)
Pages: 624-630
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[Journal Article] Redundant roles of Sox17 and Sox18 in postnatal angiogenesis in mice2006
Author(s)
Matsui, M., Kanai-Azuma, M., Hara K., Matoba, S., Hiramatsu, R., Kawakami, H., Kurohmaru, M., Koopman, P., Kanai Y
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Journal Title
J. Cell Sci 119(17)
Pages: 3513-3526
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[Journal Article] Crucial role of the small GTPase ARF6 in hepatic cord formation during liver development2006
Author(s)
Suzuki, T., Kanai Y., Hara, T., Sasaki, J., Sasaki, T., Kohara, M., Maehama, T., Taya, C., Shitara, H., Yonekawa, H., Frohman, M.A.., Yokozeki, T., Kanaho, Y
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Journal Title
Mol. Cell. Biol 26(16)
Pages: 6149-6156
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[Journal Article] Identification of Sox17 as a transcription factor that regulates oligodendrocyte development2006
Author(s)
Sohn, J., Natale, J., Chew, L-J., Belachew, S., Cheng, Y., Aguirre, A., Lytle, J., Kanai-Azuma, M., Kanai, Y., Gallo, V
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Journal Title
J. Neurosci 26(38)
Pages: 9722-9735
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[Journal Article] Influence on spatiotemporal patterns of a male-specific Sox9 activation by ectopic Sry Expression during early phases of testis differentiation in mice2005
Author(s)
Kidokoro, T., Matoba S., Hiramatsu, R., Fujisawa, M., Kanai-Azuma, M., Taya, C., Kurohmaru, M., Kawakami, H., Hayashi, Y., Kanai, Y., Yonekawa, H
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Journal Title
Dev. Biol 278(2)
Pages: 511-525
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[Journal Article] A novel Sry-downstream cellular event which preserves the readily available energy source of glycogen in mouse sex differentiation2005
Author(s)
Matoba, S., Kanai, Y., Kidokoro, T., Kanai-Azuma, M., Kawakami, H., Hayashi, Y., Kurohmaru, M
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Journal Title
J. Cell Sci 118(7)
Pages: 1449-1459
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[Journal Article] Adhesion activity of fetal gonadal cells to EGF and discoidin domains of MFG-E8, a secreted integrin-binding protein which is transiently expressed in mouse early gonadogenesis2005
Author(s)
Ishii, M., Kanai, Y., Kanai-Azuma, M., Tajima, Y., Tay, T.W., Kidokoro, T., Sanai, Y., Kurohmaru, M., Hayashi, Y
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Journal Title
Anat. Embryol 209(6)
Pages: 485-494
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