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Molecular control mechanisms of multipotential neural stem cells

Research Project

Project/Area Number 13480254
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionThe University of Tokyo

Principal Investigator

NAKAFUKU Masato  The University of Tokyo, Graduate School of Medicine, associate professor, 大学院・医学系研究科, 助教授 (80202216)

Co-Investigator(Kenkyū-buntansha) KOSAKO Hidetaka  The Institute of Medical Science, The University of Tokyo, research associate, 医科学研究所, 助手 (10291171)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥17,200,000 (Direct Cost: ¥17,200,000)
Fiscal Year 2002: ¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 2001: ¥10,600,000 (Direct Cost: ¥10,600,000)
Keywordsneural development / transcription factor / neural stem cell / neuron / glia / bHLH factor / homeodomain factor
Research Abstract

Multipotential neural stem cells serve as the origin of diverse cell types during genesis of the mammalian central nervous system (CNS). During early development, stem cells self-renew and increase their total cell numbers without overt differentiation. At later stages, the cells withdraw from this self-renewal mode, and are fated to differentiate into specific subtypes of neurons and glia in a spatially and temporally regulated manner. However, the molecular mechanisms underlying these processes remain poorly understood. In this study, we have demonstrated that the combinatorial expression and functions of a set of homeodomain-type (Pax6, Nkx2.2, Nkx6.1) and HLH-type (Olig1, Olig2, Ngn1, Ngn2, Ngn3, Mash1, Id1, Id2) play important roles in the patterned and ordered generation of multiple types of neurons and glia in the developing vertebrate central nervous system. Furthermore, we found that the same set of molecules regulate the proliferation and differentiation of neural stem cells in the adult brain and spinal cord. By applying such knowledge, we have also developed strategies to enhance latent regenerative potential of adult neural stem cells, and thereby could induce regeneration of new neurons in damaged tissues. Thus, our study has open a novel avenue of researches that link neural development during embryogenesis and its regeneration in the adult CNS.

Report

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

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Nakatomi H. et al.: "Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors"Cell. 110. 429-441 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Heins N. et al.: "Glial cells generate neurons : the role of the transcription factor Pax6"Nat. Neurosci.. 5. 308-315 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fu H.et al.: "Dual origin of spinal oligodendrocyte progenitors and evidence for the cooperative role of Olig2 and Nkx2.2 in the control of oligodendrocyte differentiation"Development. 129. 681-693 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kobayashi D. et al.: "Early subdivisions in the neural plate define distinct competence for inductive signals"Development. 129. 83-93 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kamitori K. et al.: "Cell-type-specific expression of protein tyrosine kinase-related receptor RYK in the central nervous system of the rat"Brain Res. Mol. Brain Res.. 104. 255-260 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kobayashi D. et al.: "Early subdivisions in the neural plate define distinct competence for inductive signals"Development. 129. 83-93 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fu H. et al.: "Dual origin of spinal oligodendrocyte progenitors and evidence for the cooperative role of Olig2 and Nkx2.2 in the control of oligodendrocyte differentiation"Development. 129. 681-693 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Heins N. et al.: "Glial cells generate neurons : The role of the transcription factor Pax6"Nat. Neurosci.. 5. 308-315 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakatomi H. et al.: "Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors"Cell. 110. 429-441 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kamimori K. et al.: "Cell-type specific expression f protein tyrosine kinase-related receptor RYK in the central nervous system of the rat"Mol. Brain Res.. 104. 255-266 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakatomi H. et al.: "Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors"Cell. 110. 429-441 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Heins N. et al.: "Glial cells generate neurons : the role of the transcription factor Pax6"Nat. Neurosci.. 5. 308-315 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fu H.et al.: "Dual origin of spinal oligodendrocyte progenitors and evidence for the cooperative role of Olig2 and Mkx2.2 in the control of oligodendrocyte differentiation"Development. 129. 681-693 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kobayashi D. et al.: "Early subdivisions in the neural plate define distinct competence for inductive signals"Development. 129. 83-93 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kamitori K. et al.: "Cell-type-specific expression of protein tyrosine kinase-related receptor RYK in the central nervous system of the rat"Brain Res. Mol. Brain Res.. 104. 255-260 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mizuguchi R., et al.: "Combinatorial roles of Olig2 and Neurogenin2 in the coordinated induction of pan-neuronal and subtype-specific properties of motoneurons"Neuron. 99. 757-771 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamamoto N.: "Role of Deltex-1 as a transcriptional regulator downstream of the Notch receptor"J. Biol. Chem.. 276. 45031-45040 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kato M., et al.: "Identification of Sonic hedgehog-Responsive Genes by Using cDNA Microarray"Biochem. Biophy. Res. Comm.. 289. 472-478 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kobayashi D., et al.: "Early subdivisions in the neural plate define distinct competence for inductive signals"Development. 129. 83-93 (2002)

    • Related Report
      2001 Annual Research Report

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

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