• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

前脳形成の分子機構

Research Project

Project/Area Number 13138202
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe Institute of Physical and Chemical Research (2002-2004)
Kumamoto University (2001)

Principal Investigator

相沢 慎一  独立行政法人理化学研究所, ボディプラン研究グループ, グループディレクター (60073011)

Co-Investigator(Kenkyū-buntansha) 須田 容子  独立行政法人理化学研究所, ボディプラン研究グループ, 研究員 (90201582)
高崎 延佳  独立行政法人理化学研究所, ボディプラン研究グループ, 研究員 (00342808)
黒川 大輔  独立行政法人理化学研究所, ボディプラン研究グループ, 研究員 (40342779)
村田 卓也  独立行政法人理化学研究所, ボディプラン研究グループ, 研究員 (70305001)
木村 淳  独立行政法人理化学研究所, ボディプラン研究グループ, 研究員 (70391935)
Project Period (FY) 2001 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥239,100,000 (Direct Cost: ¥239,100,000)
Fiscal Year 2004: ¥57,600,000 (Direct Cost: ¥57,600,000)
Fiscal Year 2003: ¥59,000,000 (Direct Cost: ¥59,000,000)
Fiscal Year 2002: ¥59,500,000 (Direct Cost: ¥59,500,000)
Fiscal Year 2001: ¥63,000,000 (Direct Cost: ¥63,000,000)
KeywordsOtx2 / Emx2 / Pax6 / ヘッドオーガナイザー / Shisa / 頭部誘導 / エンハンサー / 脳領域化 / 脊椎動物の進化 / 前後軸 / 前脳 / 中脳 / Otx / Emx / 新規遺伝子 / 頭部形成 / 変異マウス / Otx1 / Emx1 / ロンボメアー1 / 2 / 間脳形成 / 原皮質形成 / 新皮質形成
Research Abstract

頭部誘導に関わる新規遺伝子shisaについての解析をすすめた。Shisaは2つの後方化シグナル、WNTとFGFシグナルを抑制することによって頭部形成に働くことにおいてユニークであった;これまでヘッドオーガナイザーでFGFシグナルの拮抗因子は知られていない。Shisaはまたその作用の分子機構においてユニークであった;Shisaはシグナルを受ける細胞の小胞体でFz, FGFレセプターの成熟を制御することによりこれらシグナルの制御に働く。また、マウス頭部誘導におけるShisaとdikkopの共同作用を明らかにし、3つのshisa相同体についての機能解析も進めた。
マウス頭部形成の各段階でOtx2発現を制御するエンハンサーを同定、各脊椎動物での比較発生学的解析を、特にAN及びFMエンハンサーに注目して進めた。ANエンハンサーは誘導された吻側神経外胚葉での発現を制御し、このOtx2発現は誘導された吻側神経板の後方化(後脳化)抑制に働いている。一方、FMエンハンサーは5体節期以降、中脳及び原皮質を含む前脳尾側部の後方化(後脳化)抑制に働いている。ANエンハンサーはカエルには存在するがゼブラフィッシュ、フグには存在せず、これに対しFMエンハンサーは硬骨魚に存在する。興味あることにゼブラフィッシュFMエンハンサーはマウスでANエンハンサー活性を持つ。それぞれのゼブラフィッシュでの活性など解析を進めた。また、これらエンハンサーの起源を求めて、シーラカンス、エイ、ヤツメウナギでのゲノム解析を進めた。
誘導された吻側神経外胚葉の最初の領域化は4-6体節期 中脳、前脳後方部、前脳吻側部の3領域への分化として起こること、原皮質は新皮質、皮質下部を生じる前脳吻側部ではなく、前視蓋、視床、前視床を生じる前脳尾側部より生じること、前濃尾側部の形成にEmx2とPax6は相補的にOtx2と協働することを明らかにした。

Report

(4 results)
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (37 results)

All 2005 2004 Other

All Journal Article (12 results) Publications (25 results)

  • [Journal Article] A type I DnaJ homolog, DjA1 regulates androgen receptor signaling and spermatogenesis.2005

    • Author(s)
      Terada, K., et al.
    • Journal Title

      EMBO J 24

      Pages: 611-622

    • Related Report
      2004 Annual Research Report
  • [Journal Article] cfm is a novel gene uniquely expressed in developing forebrain and midbrain, but its null mutant exhibits no obvious phenotype.2005

    • Author(s)
      Hirano, M., et al.
    • Journal Title

      Gene Expression Patterns 5

      Pages: 439-444

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Shisa Promotes Head Formation throuth the Inhibition of Receptor Protein Maturation for the Caudalizing Factors, Wnt and FGF2005

    • Author(s)
      Yamamoto, A., et al.
    • Journal Title

      Cell 120

      Pages: 223-235

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Characterization of Opr-deficiency in mouse brain : subtle defects in dorsomedial telencephalon and medioventral forebrain2005

    • Author(s)
      Furushima, K., et al.
    • Journal Title

      Developmental Dynamics (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Characterization of the pufferfish Otx2 cis-regulators reveals evolutionarilyconserved genetic mechanisms for vertebrate head specification.2004

    • Author(s)
      Kimura-Yoshida, C., et al.
    • Journal Title

      Development 131

      Pages: 57-71

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Germinal center-associated nuclear protein contributes to affinity maturation of B cell antigen receptor in T cell-dependent responses.2004

    • Author(s)
      Kuwahara, K., et al.
    • Journal Title

      Proc.Natl.Acad.USA. 101

      Pages: 1010-1015

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Emx1 and Emx2 cooperate in initial phase of archipallium development.2004

    • Author(s)
      Shinozaki, K., et al.
    • Journal Title

      Mechanisms of Development 121

      Pages: 475-489

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Regulation of Otx2 expression and its functions in mouse epiblast and anterior neuroectoderm.2004

    • Author(s)
      Kurokawa, D., et al.
    • Journal Title

      Development 131

      Pages: 3307-3317

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Regulation of Otx2 expression and its functions in mouse forebrain and midbrain.2004

    • Author(s)
      Kurokawa, D., et al.
    • Journal Title

      Development 131

      Pages: 3319-3331

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Targeted disruption of the mouse ELYS gene results in embryonic I ethality at peri-implantation development.2004

    • Author(s)
      Okita, K., et al.
    • Journal Title

      Genes to Cells 9

      Pages: 1083-1091

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Increased Serum Leptin Protects From Adiposity Despite the Increased Glucose Uptake in White Adipose Tissue in Mice Lacing p85α Phosphoinositide 3-Kinase.2004

    • Author(s)
      Terauchi, Y., et al.
    • Journal Title

      Diabetes 53

      Pages: 2261-2270

    • Related Report
      2004 Annual Research Report
  • [Journal Article] ang is a novel gene expressed in early neuroectoderm, but its null mutant exhibits no obvious phenotype.2004

    • Author(s)
      Murata, T., et al.
    • Journal Title

      Gene Expression Patterns 5

      Pages: 171-178

    • Related Report
      2004 Annual Research Report
  • [Publications] Saito, T., et al.: "Notch2 Is Preferentially Expressed iin Mture B Cells and Indispensable for Marginal Zone B Lineage Development."Immunity. 18. 675-685 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Terauchi, Y., et al.: "Impact of Genetic Background and Ablation of Insulin Receptor Sustrate(IRS)-3 on IRS-2 Knock-out Mice."The Journal of Biological Chemistry. 278. 14284-14290 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Terada, K., et al.: "Expression of Tom34 Splicing Isoforms in Mouse Testus and Knockout of Tom34 in Mice."J.Biochem.. 133. 625-631 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Wakabayashi, Y., et al.: "Bcl11b is required for differentiation and survival of α β T lymphocytes."Nature Immunology. 4. 533-539 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] UMEZU, T., et al.: "CHARACTERIZATION OF NEWLY ESTABLISHED CLONAL OVIDUCTAL CELL LINES AND DIFFERENTIAL HORMONAL REGULATION OF GENE EXPRESSION."In Vitro Cell.Dev.Biol.-Animal. 39. 146-156 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nishida, A., et al.: "Otx2 homeobox gene controls retinal photoreceptor cell fate and pineal gland development."Nature Neuroscience. 6. 1255-1263 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hirabayashi, Y., et al.: "Evaluation of nonthreshold Ieukemogenic response to methyl nitrosourea in p53-deficienct C3H/He mice."Toxicology and Applied Pharmacology. 190. 251-261 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kuwahara, K., et al.: "Germinal center-associated nuclear protein contributes to affinity maturation of B cell antigen receptor in T cell-dependent responses."Proc.Natl.Acad.USA.. 10. 1073-1078 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kimura-Yoshida, C., et al.: "Characterization of the pufferfish Otx2 cis-regulators reveals evolutionarily conserved genetic mechanisms for the vertebrate head specification."Development. 131. 57-71 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Furukawa, T., et al.: "Otx2 homeobox gene controls retinal photoreceptor cell fate and pineal gland development."Nature Neurosci. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kurokawa, D., et al.: "Regulation of Otx2 expression and its functions in mouse epiblast and anterior neuroectoderm."Development. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kurokawa, D., et al.: "Regulation of Otx2 expression and its functions in mouse forebrain and midbrain."Development. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Inui, S., et al.: "BCR signal through a4 is involved in S6 kinase activation and required for B cell maturation including isotype switching and V region somatic hypermutation"International Immunology. 14. 177-187 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shinozaki, K., et al.: "Absence of Cajal-Retzius cells and subplate neurons associated with defect of tangential cell migration from ganglionic eminence in Emx1/2 double mutant cerebral cortex"Development. 129. 3479-3492 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hide, H., et al.: "Genetic modifiers of otocephalic phenotypes in Otx2 heterozygous mutant mice"Development. 129. 4347-4357 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hirabayashi, Y., et al.: "Serial Transplantation of p53-Deficient Hemopoietic Progenitor Cells to Assess Their Infinite Growth Potential"Exp Biol Med. 227. 474-479 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hanazono, M., et al.: "Establishment of an androgen-responsive prostanic cell line "PEA5" from a p53-deficient mouse"The Prostate. 46. 214-225 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Suda, Y., et al.: "Emx2 directs the development of diencephalon in cooperation with Otx2"Development. 128. 2433-2450 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kimura, C., et al.: "Complementary Functions of Otx2 and Cripto in Initial Patterning of Mouse Epiblast"Developmental Biology. 235. 12-32 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ino, M., et al.: "Functional disorders of the sympathetic nervous system in mice lacking the a1B subunit (Cav2.2) of N-type calcium channels"PNAS. 98. 5323-5328 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kaji, T., et al.: "Establishment of Left-Right Asymmetic Innervation in the Lancelet Oral Region"The Journal of Comparative Neurology. 435. 394-405 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Myojin, M., et al.: "Isolation of Dlx and Emx Gene Congnates in an Agnathan Species, Lampetra japonica, and Their Expression Patterns During Embryonic and Larval Development : Conserved and Diversified Regulatory Patterns of Homeobox Genes in Vertebrate Head Evolution"Journal of Experimental Zoology (MOL DEV EVOL). 291. 68-84 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tamura, T., et al.: "Impairment in the Expression and Activity of Gyn During Differentiation of Naive CD4+ T Cells into the Th2 Subset"The Journal of Immunology. 167. 1962-1969 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tian, E., et al.: "Otx2 Is Required to Respond to Signals from Anterior Neural Ridge for Forebrain Specification"Developmental Biology. 242. 204-223 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Inui, S., et al.: "BCR signal through a4 is involved in S6 kinase activation and required for B cell maturation including isotype switching and V region somatic hypermutation"International Immunology. 14. 177-187 (2001)

    • Related Report
      2001 Annual Research Report

URL: 

Published: 2001-04-01   Modified: 2018-03-28  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi