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Analysis of the Notch-HES pathway that regulates mammalian neurogenesis

Research Project

Project/Area Number 09670009
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General anatomy (including Histology/Embryology)
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

ISHIBASHI Makoto  Kyoto Univ.Graduate School of Medicine, Dept.of Anat.& Develop.Biol., Lecturer, 医学研究科, 助手 (30232341)

Co-Investigator(Kenkyū-buntansha) SHIOTA Kohei  Kyoto Univ.Graduate School of Medicine, Dept.of Anat.& Develop.Biol., Professor, 医学研究科, 教授 (80109529)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
KeywordsNeural precursor cell / Differentiation / Transcriptional regulation / Myogenesis / HES / Notch / Gene targeting / 神経分化 / 脳 / 網膜 / マウス胎児 / ノックアウトマウス
Research Abstract

In order to elucidate the transcriptional regulation of mammalian neurogenesis, we analyzed the roles HES-1, which is a mammalian homolog of Drosophila hairy and Enhancer of split genes, in neurogenesis and obtained the following results.
1. HES-l was intensely expressed in immature tissues of rodent embryos, including neural and muscular tissues, and the expression level declined along with tissue differentiation.
2. HES- 1 suppressed the differentiation of cultured myogenic cells which is mediated by Myo-D.
3. When HES-l was induced in neural precursor cells in the central nervous system of mouse embryos, it completely inhibited neuronal differentiation.
4. In mice lacking HES-1, the expression of Mashl increased and premature neurogenesis occurred. These mice had cranial neural tube defects resulting from the failure of neural tube closure.
5. When the retinal tissue of fetal mice lacking HES-l was cultured in vitro, the neural retina showed premature and abnormal differentiation.
6. From an in vitro promotor analysis of mouse HES-1 gene, it was revealed that HES-1 expression is regulated by itself (negative autoregulation).
From these observations, it was concluded that HES-I negatively regulates mammalian neurogenesis.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] 石橋 誠 他: "Heat shock-induced homeotic transformation of the axial skeleton and associated shifts of HOX gene expression domains in mouse embryos." Reproductive Toxicology. 11. 761-770 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 石橋 誠 他: "Structure, chromosomal locus, and promoter of mouse Hes2 gene, a homologue of Drosophila hairy and Enhancer of split." Genomics. 49. 69-75 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 石橋 誠 他: "bHLH transcription factors and mammalian neuronal differentiation." International Journal of Biochemistry and Cell Biology. 29. 1389-1399 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 塩田 浩平 他: "SoxD : an essential mediator of induction of anterior neural tissues in Xenopus embryos." Neuron. 21. 77-85 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 塩田 浩平 他: "Normal and abnormal neurulation in human embryos : Implications for the pathogenesis of neural tube defects." Neuropathology. 18. 415-418 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 塩田 浩平 他: "Differences in axial curvature correlate with species-specific rate of neural tube closure in the embryo of rabbit, rat, chick and human." Anatomy and Embryology. 198. 185-194 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ishibashi, M., Shiota, K.et al.: "Heat shock-induced homeotic transformation of the axial skeleton and associated shifts of HOX gene expression domains in mouse embryos." Reproductive Toxicology. 11. 761-770 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ishibashi, M.et al.: "Structure, chromosomal locus, and promoter of mouse Hes2 gene, a homologue of Drosophila hairy and Enhancer of split." Genomics. 49. 69-75 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ishibashi, M.et al.: "bHLH transcription factors and mammalian neuronal differentiation." International Journal of Biochemistry and Cell Biology.29. 1389-1399 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shiota, K.et al.: "SoxD : an essential mediator of induction of anterior neural tissues in Xenopus embryos." Neuron. 21 (1). 77-85 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shiota, K.et al.: "Normal and abnormal neurulation in human embryos : Implications for the pathogenesis of neural tube defects." Neuropathology. 18. 415-418 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shiota, K.et al.: "Differences in axial curvature correlate with species-specific rate of neural tube closure in the embryo of rabbit, rat, chick and human." Anatomy and Embryology. 198. 185-194 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 塩田浩平 他: "Normal and abnormal neurulation in human embryos:Implications for the pathogenesis of neural tube defects." Neuropathology. 18. 415-418 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 水関健司 他: "SoxD:an essential mediator of induction of anterior neural tissues in Xenopus embryos." Neuron. 21(1). 77-85 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Peeters,M.C.E.他: "Differences in axial curvature correlate with species-specific rate of neural tube closure in the embryo of rabbit,rat,chick and human." Anatomy and Embryology. 198(3). 185-194 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 須田道雄 他: "Skeletal overgrowth in transgenic mice that overexpress brain natriuretic peptide." Proc.Natl.Acad.Sci.USA. 95. 2337-2342 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kagayama,R., Ishibashi,M., Takebayashi,K., and Tomita,K.: "bHLH transcription factors and mammalian neuronal differentiation." Int.J.Biochem.Biol.(in press). (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nishimura,M., Isaka,F., Ishibashi,M., Tomita,K., Tsuda,H., Nakanishi,S., and Kageyama,R.: "Structure,chromosomal lucus,and promoter of mouse Hes2 gene,a homologue of Drosophia hairty and Enhancer of split." Genomics. (in press). (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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