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Organizing signal and the tectal and cerebellar differentiation

Research Project

Project/Area Number 13480243
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Developmental biology
Research InstitutionTohoku University

Principal Investigator

NAKAMURA Harukazu  Graduate School of Life Sciences, Professor, 大学院・生命科学研究科, 教授 (90079690)

Co-Investigator(Kenkyū-buntansha) SATO Tatsuya  Society for the promotion of Science, Postdoctoral fellow, Japan, 大学院・生命科学研究科, 日本学術振興会特別研究員
WATANABE Yuji  Graduate School of Life Sciences, Assistant Professor, 大学院・生命科学研究科, 助手 (80301042)
FUNAHASHI Junichi  Institute of Development, Aging and Cancer, Associate Professor, 加齢医学研究所, 助教授 (00270827)
木村 淳  東北大学, 加齢医学研究所, 非常勤研究員
杉山 清佳  東北大学, 大学院・生命科学研究科, 日本学術振興会特別研究員
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥15,100,000 (Direct Cost: ¥15,100,000)
Fiscal Year 2002: ¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 2001: ¥8,000,000 (Direct Cost: ¥8,000,000)
Keywordsmesencephaon / metencephalon / organizer / Fgf8 / Ras-ERK signaling pathway / cerebellar differentiation / Fgf8a / Fgf8b / Otx2 / Glx2 / Irx2 / 視蓋 / 小脳
Research Abstract

The isthmus works as an organizer, and Fgf8 mimics the organizing activity. The isthmic organizer plays a role for the development of the tectum and the cerebellum in the mesencephalon and in the metencephalon, respectively. It is very interesting that completely different architecture of the tectum and the cerebellum differentiates under a common signal. We paid attention to that among 8 isoforms of Fgf8, Fgf8a and Fgf8b are expressed in the isthmus, and carried out misexpression of Fgf8a and Fgf8b by in ovo electroporation. Fgf8a induced the tectum in the diencephalon as expected. It was surprising that Fgf8b changed the fate of the mesencephalic alar plate to the cerebellum. Fgf8b repressed Otx2 expression in the mesencephalon, but induced expression of Gbx2 and Irx2, which are normally expressed in the metencephalon. The quantitative study revealed that the difference between Fgf8a and Fgf8b could be attributed to the difference in the intensity of the signal. It was suggested that strong signal of Fgf8 turns the gene expression cascade toward the cerebellar differentiation.
We were then interested in Ras-ERK pathway as the signal transduction pathway downstream of the Fgf8 signal. In normal embryos ERK is activated at the site where Fgf8 mRNA is localized. Fgf8b activated ERK while Fgf8a or lower dose of Fgf8b did not activate ERK in the mes/metencephalon. Disruption of the Ras-ERK signaling pathway by dominant negative form of Ras (Ras^<S17N>) changed the fate or the metencephalic alar plate from cerebellum to tectum. Ras^<S17N> canceled the effects of Fgf8b, while co-transfection of Fgf8a and Ras^<S17N> exerted additive effects. The results indicate that the presumptive metencephalon receives strong Fgf8 signal that activates the Ras-ERK pathway and differentiates into the cerebellum.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] Sugiyama, S., Nakamura, H.: "The role of Grg4 in tectal laminar formation"Development. 130. 451-462 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsunaga, E., Katahira, T., Nakamura, H.: "Role of Lmx1b and Wnt1 in mesencephalon and metencephalon development"Development. 129. 5269-5277 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kishimoto, K.N., Watanabe, Y., Nakamura, H., Kokubun, S.: "Ectopic bone formation by electroporatic transfer of bone morphogenetic protein-4 gene"Bone Aug.. 31・2. 340-347 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sato, T., Araki, I., Nakamura, H.: "Inductive signal and tissue responsiveness to define the tectum and the cerebellum"Development. 128. 2461-2469 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsunaga, E., Araki, I., Nakamura, H.: "Role of Pax3/7 in the tectum regionalization"Development. 128. 4069-4077 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura, H.: "Regionalisation and polarity formation of the optic tectum"Prog. Neurobiol. 65. 473-488 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura, H.: "Regionalisation of the optic tectum : Combination of the gene expression that defines the tectum"Trends Neurosci.. 24. 32-39 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura, H., Funahashi J.: "DNA introduction into chick embryos by in ovo electroporation"Methods. 24. 43-48 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 松永英治, 仲村春和: "視蓋領域形成におけるPax6とPax3/7の役割"実験医学増刊. 20・5. 34-40 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 仲村春和: "中枢神経系の領域はどのようにして形成されるか"実験医学増刊. 20・5. 12-20 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 佐藤達也, 仲村春和: "視蓋/小脳の分化とFGFシグナル"実験医学増刊. 20・2. 213-220 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 松永英治, 仲村春和: "視蓋領域形成におけるPax6とPax3/7の役割"実験医学増刊. 20・5. 34-40 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 仲村春和: "中枢神経系の領域はどのようにして形成されるか"実験医学増刊. 20・5. 12-20 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 佐藤達也, 仲村春和: "視蓋/小脳の分化とFGFシグナル"実験医学増刊. 20・2. 213-220 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 仲村春和, 村上富士夫: "実験医学増刊 脳・神経研究のフロンティア"羊土社. 207 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sato,T, Araki,I, Nakamura,H.: "Inductive signal and tissue responsiveness to define the tectum and the cerebellum"Development. 128. 2461-2469 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsunaga,E., Araki,I, Nakamura,H.: "Role of Pax3/7 in the tectum regionalization"Development. 128. 4069-4077 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ye W, Bouchard M, Stone D, Liu X, Vella F, Lee J, Nakamura H, Ang SL, Busslinger M, Rosenthal A: "Distinct regulators control the expression of the midhindbrain organizer signal FGF8"Nat Neurosci. 4. 1175-1181 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kishimoto KN, Watanabe Y, Nakamura H, Kokubun S: "Ectopic bone formation by electroporatic transfer of bone morphogenetic protein-4 gene"Bone. Aug 31(2). 340-347 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsunaga,E., Katahira,T., Nakamura,H.: "Role of Lmxlb and Wntl in mesencephalon and metencephalon development"Development. 129. 5269-5277 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugiyama,S., Nakamura,H.: "The role of Grg4 in tectal laminar formation"Development. 130. 451-462 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Harukazu Nakamura: "Regionalisation of the optic tectum: Combination of the gene expression that defines the tectum"Trends Neurosci. 24. 32-39 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Harukazu Nakamura, Jun-ichi Funahashi, G. Eichele, ed.: "Introduction of DNA into chick embryos by in ovo electroporation"Methods(Academic Press). 24. 43-48 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Harukazu Nakamura: "Regionalisation and polarity formation of the optic tectum"Prog.Neurobiol.. 65. 473-488 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugiyama, S., Nakamura, H.: "The role of Grg4 in tectal laminar formation"Development. 130. 451-462 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsunaga, E., Katahira, T., Nakamura.H.: "Role of Lmx1b and Wnt1 in mesencephalon and metencephalon development"Development. 129. 5269-5277 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kishimoto, K.N., Watanabe, Y., Nakamura, H., Kokubun, S.: "Ectopic bone formation by electroporatic transfer of bone morphogenetic protein-4 gene"Bone Aug.. 31・2. 340-347 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 松永英治, 仲村春和: "視蓋領域形成におけるPax6とPax3/7の役割"実験医学増刊. 20・5. 34-40 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 仲村春和: "中枢神経系の領域はどのようにして形成されるか"実験医学増刊. 20・5. 12-20 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 佐藤達也, 仲村春和: "視蓋/小脳の分化とFGFシグナル"実験医学増刊. 20・2. 213-220 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sato, T., Araki, I., Nakamura, H.: "Inductive signal and tissue responsiveness to define the tectum and the cerebellum"Development. 128. 2461-2469 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Matsunaga, E., Araki, I., Nakamura, H.: "Role of Pax3/7 in the tectum regionalization"Development. 128. 4069-4077 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ye, W., Bouchard, M., Stone, D., Liu, X., Vella, F., Lee, J., Nakamura, H., Ang.SL., Busslinger, M., Rosenthal, A.: "Distinct regulators control the expression of the midhindbrain organizer signal FGF8"Nat Neurosci.. 4. 1175-1181 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakamura, H.: "Regionalisation of the optic tectum : Combination of the gene expression that defines the tectum"Trends Neurosci.. 24. 32-39 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakamura, H., Funahashi, J.: "Introduction of DNA into chick embryos by in ovo electroporation"Methods. 24. 43-48 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakamura, H.: "Regionalisation and polarity formation of the optic tectum"Prog. Neurobiol.. 65. 473-488 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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