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Development of methods for specifically inhibit FGF signalling system in vivo

Research Project

Project/Area Number 05558100
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 神経・脳内生理学
Research InstitutionUniversity of Tokyo

Principal Investigator

OKAMOTO Harumasa  Univ.Tokyo, Fac.Med., Assoc.Prof., 医学部(医), 助教授 (40134283)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Kunitaro  Univ.Tokyo, Fac.Med., Professor, 医学部(医), 教授 (10010034)
KENGAKU Mineko  Univ.Tokyo, Fac.Med., DC fellow of Japanese Society for the Promotion of Science, 医学部(医), 日本学術振興会特別研
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1994: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1993: ¥4,900,000 (Direct Cost: ¥4,900,000)
KeywordsFGF / FGF receptor / Dominant-negative mutation / Xenopus laevis / Tyrocine kinase / 線維芽細胞成長因子 / ツメガエル / 単クローン抗体 / 神経誘導
Research Abstract

Recently, fibroblast growth factor (FGF) has been shown to play a crucial role in the development, differentiation and maintenance of neuronal cells in vitro.
However, we do not know yet whether FGF plays a similar crucial role in the nervons system in vivo. To address this issue, we may need methods to inhibit the action of FGF specifically and without toxic effects. Introduction of dominant-negative form of FGF receptor into cells of interest seems a promising method in this respect. We choose developing embryos of Xenopus laevis as a model system to examine the availability of the method, in whid FGF acts as a neural inducer.
It has been reported that two distinct types of FGF receptor named XFGFR-1 and XFGFR-2 are expressed in Xenopus embryo. In the present research, we have cloned three new FGF receptor cDNAs from Xenopus gastrula, which we designated XFGFR-3, XFGFR-4 and XFGFR-5 based on their homology to the human FGF receptors FGFR-3 and FGFR-4, respectively (XFGFR-5 is highly homologous, but distinct from XFGFR-4) . To identify the Xenopus FGFreceptor subtype (s) which is involved in neural induction, we have determined the spatio-temporal expression patterns of these FGF receptors by RT-PCR and RNase protection assay, and found that XFGFR-2,4 and 5 were expressed at the right time and right place for the neural induction during early development. We have made dominant-negative form of these cDNAs, in which cytoplasmic tyrosine kinase domain is deleted. Detailed studies using these dominant-negative moleculess are in progress.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] 岡本治正: "アフリカツメガエル:神経細胞の誘導" BRAIN MEDICAL. 6. 143-150 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mineko Kengaku: "Morphogenetic action of basic FGF in determining anteroposterior axis in the developing central nervous system of Xenopus laevis." Society for Neuroscience Abstracts. 20,254. 20. 254-254 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mineko Kengaku: "bFGF as a possible neural-inducing morphogen." Neurosci. Res, Suppl.19. S7-S7 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ikuko Hongo: "Identification of the Xenopus FGFR subtype(s)involved in neural induction." Neurosci. Res, Suppl.19. S116-S116 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kengaku, M.Okamoto, H.: "Basic fibroblast growth factor induces differentiation of neural tube and neural crest lineages of cultured ectoderm cells from Xenopus gastrula." Development. 119. 1067-1078 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kengaku, M.Okamoto, H.: "The neural crest-and the neural tube-inducing pathways are differentially mediated in gastrula ectoderm cells as revealed by staurosporin, a protein kinase C inhibitor." Jpn.J.Physiol. 43, Suppl.2. S299 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kengaku, M.Okamoto, H.: "Basic FGF determines the anterior-posterior axis during early neural development in Xenopus." Neurosci.Res.Suppl.18. S119 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kengaku, M.Okamoto, H.: "Morphogenetic action of basic FGF in determining anteroposterior axis in the developing central nervous system of Xenopus laevis." Society for Neuroscience Abstracts.20. 254 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kengaku, M.Okamoto, H.: "bFGF as a possible neural-inducing morphogen." Neurosci.Res.Suppl.19. S7 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hongo, I.Mohd.A.M.Sugaya, M.Kengaku, M.Okamoto, H.: "Indentification of the Xenopus FGFR subtype (s) involved in neural induction." Neurosci.Res. Suppl.19. S116 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nishizawa, K.Okamoto, H.: "Mutation analysis of the role for the carboxy-terminus encoding region in NGF-induced stabilization of GAP-43 mRNA." Biophys.Biochem.Res.Commun. 205. 1380-1385 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 岡本治正: "アフリカツメガエル:神経細胞の誘導" BRAIN MEDICAL. 6. 143-150 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Mineko Kengaku: "Morphogenetic action of basic FGF in determining anteroposterior axis in the developing central nervous system of Xenopus laevis." Society for Neuroscience Abstracts.20,254. 20. 254-254 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Mineko Kengaku: "bFGF as a possible neural-inducing morphogen." Neurosci.Res.,Suppl.19. S7-S7 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ikuko Hongo: "Identification of the Xenopus FGFR subtype(s)involved in neural induction." Neurosci.Res.,Suppl.19. S116-S116 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kengaku,M.: "Basic fibroblast growth factor induces differentiation of neural tube and neural crest lineages of cultured ectcderm cells from Xenopus gastrula." Development. 119. 1078 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kengaku,M.: "The neural crest-and the neural tube-inducing pathways are differentially mediated in gastrula ectoderm cells as revealed by staurosporin,a protein kinase C inhibitor." Japanese Journal of Physiology. 43,Suppl.2. S299 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kengaku,M.: "Basic FGF determines the anterior-posterior axis during early neural development in Xenopus." Neuroscience Research. Suppl.18. S119 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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