Functional analysis of the Wnt signal promoting factor Tsh3 in early embryogenesis

• Project/Area Number: 19370097
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Developmental biology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: SASAI Yoshiki The Institute of Physical and Chemical Research, 細胞分化・器官発生研究グループ, グループディレクター (20283616)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2008: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000); Fiscal Year 2007: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
• Keywords: Tsh3 / Wnt / β-catenin / 体軸形成 / Znフィンガー / 転写制御 / 胚発生 / アフリカツメガエル / beta-catenin / 転写因子 / 核内因子 / 初期発生

Research Abstract

代表研究者らはアフリカツメガエルの系を用いて、核内ZnフィンガータンパクTsh3が初期胚体軸極性を制御する必須因子であることを見いだした。Tsh3の機能阻害では、背側体軸の形成が著しく阻害され、腹側化した胚が発生する。機能亢進及び機能阻害実験からWntシグナルを細胞内で活性化することが明らかになった。Luciferaseアッセイから、Tsh3はs-cateninによる核内での標的遺伝子の発現活性化を促進することも判明した。タンパクレベルの解析から、Tsh3はs-cateninに結合し、直接あるいは間接的にその活性を正に制御することがその機序であることも示唆された。Tsh3はsperm entryによって誘導された背側での弱いWntシグナル活性をブーストして、明確な体軸形成につなげる増幅系に関与している可能性が高い。

Research Products

• [Journal Article] Twisted gastrulation mutation suppresses skeletal defect phenotypes in Crossveinless 2 mutant mice (2008)
  • Author(s): Ikeya M, Nosaka T, Fukushima K, Kawada M, Furuta Y, Kitamura T, Sasai Y.
  • Journal Title: Mech Dev. 125 Pages: 832-842
  • Peer Reviewed
• [Journal Article] Ectodermal Factor Restricts Mesoderm Differentiation by Inhibiting p53 (2008)
  • Author(s): Sasai, N., Yakura, R,, Kamiya, D., Nakazawa, Y. and Sasai, Y.
  • Journal Title: Cell 133 Pages: 878-890
  • Peer Reviewed
• [Journal Article] Robust Stability of the Embryonic Dorsal Axial Pattern Requires ONT1, a Secreted Scaffold for Chordin Degradation (2008)
  • Author(s): Inomata, H., Haraguchi, T. and Sasai, Y.
  • Journal Title: Cell 134 Pages: 854-865
  • Peer Reviewed
• [Journal Article] Robust Stability of the Embryonic Dorsal Axial Pattern Requires ONT1, a Secreted Scaffold for Chordin Degradation (2008)
  • Author(s): Hidehiko Inomata
  • Journal Title: Cell 134 Pages: 854-865
  • Peer Reviewed
• [Journal Article] Ectodermal Factor Restricts Mesoderm Differentiation by Inhibiting p53 (2008)
  • Author(s): Noriaki Sasai
  • Journal Title: Cell 133 Pages: 878-890
  • Peer Reviewed
• [Journal Article] Twisted gastrulation mutation suppresses skeletal defect phenotypes in Crossveinless 2 mutant mice (2008)
  • Author(s): Makoto Ikeya
  • Journal Title: Mechanisms of Development 125 Pages: 832-842
  • Peer Reviewed
• [Journal Article] The secreted EGF-Discoidin factor xDel1 is essential for dorsal development of the Xenopus embryo (2007)
  • Author(s): Arakawa, A., Matsuo-Takasaki, M., Takai, A., Inomata, H., Matsumura, M., Ikeya, M., Takahashi, K., Miyachi, Y., Sasai, N. and Sasai,Y.
  • Journal Title: Developmental Biology 306 Pages: 160-169
  • Peer Reviewed
• [Journal Article] XTsh3 is an essential enhancing factor of canonical Wnt signaling in Xenopus axial determination (2007)
  • Author(s): Onai, T., Matsuo-Takasaki, M., Inomata, H., Aramaki, T., Matsumura, M., Yakura, R., Sasai, N., and Sasai, Y.
  • Journal Title: EMBO J 26 Pages: 2350-2360
  • Peer Reviewed
• [Journal Article] XTsh3 is an essential enhancing factor of canonical Wnt signaling in Xenopusaxial determination. (2007)
  • Author(s): Takayuki Onai
  • Journal Title: EMBO Journal 26 Pages: 2350-2360
  • Peer Reviewed
• [Journal Article] The secreted EGF-Discoidin factor xDell is essntial for dorsal development of the Xenopus embryo. (2007)
  • Author(s): Akiko Arakawa
  • Journal Title: Developmental Biology 306 Pages: 160-169
  • Peer Reviewed
• [Presentation] Xenopus ONT1 is novel secreted pro-BMP factor that restricts Chordin in axial development (2008)
  • Author(s): 猪股秀彦
  • Organizer: 41^<st> Annual Meeting for the Japanese Society of Developmental Biology
  • Place of Presentation: 徳島県郷土文化会館
  • Year and Date: 2008-05-28
• [Presentation] Ectodermal specification by a novel transcriptional modulator (2008)
  • Author(s): 笹井紀明
  • Organizer: 41^<st> Annual Meeting for the Japanese Society of Developmental Biology
  • Place of Presentation: 徳島県郷土文化会館
  • Year and Date: 2008-05-28
• [Presentation] Ectodermal specification by a novel transcriptional modulator (2008)
  • Author(s): 笹井紀明
  • Organizer: 41^<st> Annual Meeting for the Japanese Society of Developmental Biologists
  • Place of Presentation: 徳島県郷土文化会館
  • Year and Date: 2008-05-28
• [Presentation] Xenopus ONT1 is novel secreted pro-BMP factor that restricts Chordin in axial development (2008)
  • Author(s): 猪股秀彦
  • Organizer: 41^<st> Annual Meeting for the Japanese Society of Developmental Biologists
  • Place of Presentation: 徳島県郷土文化会館
  • Year and Date: 2008-05-28
• [Remarks]
  • URL: http://www.cdb.riken.jp/jp/index.html