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2004 Fiscal Year Final Research Report Summary

Fate determination of neural stem cells and analysis of the regulatory mechanisms for neuronal characteristic acquisition

Research Project

Project/Area Number 12210013
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKeio University (2001-2004)
Osaka University (2000)

Principal Investigator

OKANO Hideyuki  Keio University, School of Medicine, Department of Physiology, Professor, 医学部, 教授 (60160694)

Project Period (FY) 2000 – 2004
Keywordsneural stem cell / self renewal / Notch-signaling / Musashi / neuronal differentiation / neurosphere / regenerative medicine / Drosophila
Research Abstract

We have investigated how Notch signaling and musashi that has been suggested to potentiate Notch signaling activity by translationally inhibiting Notch antagonist, Numb (Imai et al., 2001), control the self-renewal and/or differentiation of neural stem cells. In addition, we have developed a system in which ES cells could be efficiently induced to differentiate into dopaminergicneuronsormotorneurons (Yoshizaki et al.2004 ; Okada et al.,2004) andatechniquetoisolateneuralstemcells that exist in ventral mesencephalon and differentiate them into TH (Tyrosine Hydoxylase) positive dopaminergicneurons, using nestin promoter EGFP Tg animal and FACS sorting (Sawamoto et al., 2001).
We first performed genetic analyses of Drosophila musashi (d-musashi) andfoundthatd-musashicouldinhibitTramtrack, which we found one of the targets of dMusashi, only in the one daughter cells where Notch signaling are not activated, and could not do so in the other daughter cells where Notch signaling are activated, t … More hereby making two daughter cells differentiate into neurons or glia, respectively (Okabe et al., 2001). We extended the analysis to mammalian d-Musashi homolog, m-musashi and found that Numb is a putative downstream target of m-musashi. In the meantime, we have also performed phenotypic analyses of m-musashi 1/2 knockout mice and demonstrated that m-musashiisrequiredfortheneural stem cells to selfrenew (Sakakibara et al., 2002). We hypothesized that m-musashi might promote selfrenewal activity of neural stem cells by potentiating the Notch signaling activity through translational inhibition of Numb. To further establish the link between the potentiation of selfrenewal activity of neural stem cells and the modulation of Notch signaling activity, both are mediated by m-musashi, wehave developedthetechniquewhichenablesustomonitorthe activity of Notch signaling and thereby examine the relationship between Musashi and the activity of Notch (Tokunaga et al., 2004 ; Koyama et al., in preparation). Less

  • Research Products

    (14 results)

All 2004 2002 2001

All Journal Article (12 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Mapping spatio-temporal activation of Notch signaling during neurogenesis and gliogenesis in the developing mouse brain.2004

    • Author(s)
      Tokunaga A, Kohyama J, Yoshida T, Nakao K, Sawamoto K, Okano H
    • Journal Title

      J Neurochem 90

      Pages: 142-154

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Retinoic acid-concentration-dependent acquisition of neural cell identity during in vitro differentiation of mouse embryonic stem cells.2004

    • Author(s)
      Okada Y, Shimazaki T, Sobue G, Okano H
    • Journal Title

      Dev Biol 275

      Pages: 124-142

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Mapping spatio-temporal activation of Notch signaling during neurogenesis and gliogenesis in the developing mouse brain.2004

    • Author(s)
      Tokunaga A., Kohyama J., Yoshida T., Nakao K., Sawamoto K., Okano H.
    • Journal Title

      J Neurochem 90(1)

      Pages: 142-154

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Retinoic acid-concentration-dependent acquisition of neural cell identity during in vitro differentiation of mouse embryonic stem cells.2004

    • Author(s)
      Okada Y., Shimazaki T., Sobue G., Okano H.
    • Journal Title

      Dev Biol 1 275(1)

      Pages: 124-142

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] RNA-binding protein Musashi family, roles for CNS stem cells and a subpopulation of ependymal cells revealed by targeted disruption and antisense ablation.2002

    • Author(s)
      Sakakibara, S., Nakamura, Y., Koike, M., Takano, H., Uchiyama, Y., Noda, T., Okano, H.
    • Journal Title

      Proc. Natl. Acad. Sci. USA 99

      Pages: 15194-15199

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] RNA-binding protein Musashi family, roles for CNS stem cells and a subpopulation of ependymal cells revealed by targeted disruption and antisense ablation.2002

    • Author(s)
      Sakakibara S., Nakamura Y., Koike M., Takano H., Uchiyama Y., Noda T., Okano H.
    • Journal Title

      Proc.Natl.Acad.Sci. USA 99

      Pages: 15194-15199

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Translational repression determines a neuronal potential in Drosophila asymmetric cell division.2001

    • Author(s)
      Okabe M, Imai T, Kurusu M., Hiromi Y, Okano H
    • Journal Title

      Nature 41

      Pages: 94-98

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Generation of dopaminergic neurons in the adult brain from mesencephalic precursor cells labeled with a nestin-GFP transgene.2001

    • Author(s)
      Sawamoto K, Nakao N, Kakishita K, Ogawa Y, Toyama Y, Yamamoto A, Yamaguchi M, Mori K, Goldman SA, Itakura T, Okano H
    • Journal Title

      J Neurosci 21

      Pages: 3895-3903

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The neural RNA-binding protein Musashil translationally regulaties the m-numb gene expression by interacting with its mRNA.2001

    • Author(s)
      Imai T, Tokunaga A, Yoshida T, Hashimoto M, Weinmaster G, Mikoshiba K, Nakafuku M, Okano H
    • Journal Title

      Mol Cell Biol 21

      Pages: 3888-3900

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Translational repression determines a neuronal potential in Drosophila asymmetric cell division.2001

    • Author(s)
      Okabe M., Imai T., Kurusu M.Hiromi Y., Okano.H.
    • Journal Title

      Nature 411

      Pages: 94-98

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The neural RNA-binding protein Musashi1 translationally regulaties the m-numb gene expression by interacting with its mRNA.2001

    • Author(s)
      Imai T., Tokunaga A., Yoshida T., Hashimoto M., Weinmaster G., Mikoshiba K., Nakafuku M., Okano H.
    • Journal Title

      Mol.Cell Biol. 21

      Pages: 3888-3900

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Generation of dopaminergic neurons in the adult brain from mesencephalic precursor cells labeled with a nestin-GFP transgene.2001

    • Author(s)
      Sawamoto K., Nakao N., Kakishita K., Ogawa Y., Toyama Y., Yamamoto A., Yamaguchi M., Mori K., Goldman S.A., Itakura T., Okano H.
    • Journal Title

      J.Neurosci. 21

      Pages: 3895-3903

    • Description
      「研究成果報告書概要(欧文)」より
  • [Patent(Industrial Property Rights)] 胚性幹細胞からの神経幹細胞、運動ニューロンおよびGABA作動性ニューロンの製造法動性ニューロンの製造法2001

    • Inventor(s)
      岡野栄之, 島崎琢也
    • Industrial Property Rights Holder
      (独)科学技術振興機構
    • Industrial Property Number
      特許、第3660601号
    • Filing Date
      2001-03-31
    • Acquisition Date
      2005-03-25
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] Musashi1によるNumb蛋白質発現抑制剤2001

    • Inventor(s)
      岡野栄之, 今井貴雄他4名
    • Industrial Property Rights Holder
      (独)科学技術振興機構
    • Industrial Property Number
      特許、第3566941号
    • Filing Date
      2001-05-31
    • Acquisition Date
      2004-06-18
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2008-05-27  

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