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Avascular environment regulates differentiation of neural stem cells

Research Project

Project/Area Number 26670097
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General anatomy (including histology/embryology)
Research InstitutionDoshisha University

Principal Investigator

Ken-ichi Mizutani  同志社大学, 脳科学研究科, 准教授 (40469929)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords神経発生 / 大脳皮質 / 活性酸素 / 血管発生 / 低酸素
Outline of Final Research Achievements

The precise control of neuronal migration and morphological changes during differentiation is essential for neocortical development. We found that the progenitors had higher levels of mitochondrial reactive oxygen species (mtROS) , but these levels significantly decreased with differentiation. A possible candidate modulator of mtROS is the Prdm16 gene, which was identified by microarray analysis. Prdm16 was specifically expressed by progenitors in the ventricular zone, but its Prdm16 expression declined as cells transitioned into NeuroD1-positive multipolar cells. This downregulation of Prdm16 expression was crucial for the appropriate progression of the multipolar phase and was required for normal cellular development. Both reporter assay and mtROS quantification demonstrated that PGC1α is a major downstream effector of Prdm16 and NeuroD1 that is required for the modulation of multipolar phase and its characteristic mode of migration.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (13 results)

All 2016 2015 2014

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Acknowledgement Compliant: 2 results) Presentation (9 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Deletion of Prdm8 impairs development of upper-layer neocortical neurons.2015

    • Author(s)
      Inoue M, Iwai R, Yamanishi E, Yamagata K, Komabayashi-Suzuki M, Honda A, Komai T, Miyachi H, Kitano S, Watanabe C, Teshima W, Mizutani K.
    • Journal Title

      Genes Cells

      Volume: 20 Issue: 9 Pages: 758-770

    • DOI

      10.1111/gtc.12274

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] NF-κB signaling regulates the generation of intermediate progenitors in the developing neocortex.2015

    • Author(s)
      Yamanishi E, Yoon K, Alberi L, Gaiano N, Mizutani K.
    • Journal Title

      Genes Cells

      Volume: 20 Issue: 9 Pages: 706-719

    • DOI

      10.1111/gtc.12267

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deletion of Prdm8 impairs the development of the upper-layer neocortical neurons.2015

    • Author(s)
      Inoue M., Iwai R., Yamanishi E., Yamagata K., Suzuki-Komabayashi M., Komai T., Miyachi H., Kitano S., Honda A., Watanabe C., Teshima W. and Mizutani K.
    • Journal Title

      Genes to Cells

      Volume: 0 Pages: 0-0

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] NF-kB signaling regulates the generation of intermediate progenitors in the developing neocortex.2015

    • Author(s)
      Yamanishi E., Keejung Y., Lavinia A., Gaiano N. and Mizutani K.
    • Journal Title

      Genes to Cells

      Volume: 0 Pages: 0-0

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 発生期大脳皮質の神経発生と血管発生の相互依存性の解析2016

    • Author(s)
      山西恵美子、渡部千里、手島羽香、岩井亮太、田畑秀典、鈴木真理子、永田浩一、原田浩、依馬正次、水谷健一
    • Organizer
      第9回神経発生討論会
    • Place of Presentation
      東京医科歯科大学
    • Year and Date
      2016-03-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] Prdm8およびその下流候補分子Ebf3は、発生期大脳皮質の神経分化を調節する2016

    • Author(s)
      岩井亮太、田畑秀典、井上真悠子、鈴木真理子、永田浩一、水谷健一
    • Organizer
      第9回神経発生討論会
    • Place of Presentation
      東京医科歯科大学
    • Year and Date
      2016-03-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] Prdm16 is critical for progression of multipolar phase during neural differentiation of the developing neocortex2016

    • Author(s)
      Ken-ichi Mizutani
    • Organizer
      第9回神経発生討論会(Japan-Korea Joint symposium)
    • Place of Presentation
      東京医科歯科大学
    • Year and Date
      2016-03-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 大脳皮質発生過程における神経と血管の相互依存性2016

    • Author(s)
      水谷健一
    • Organizer
      新学術領域「血管と神経」成果公開シンポジウム
    • Place of Presentation
      京都大学
    • Year and Date
      2016-02-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] 哺乳類大脳皮質の神経分化を制御する分子機構2015

    • Author(s)
      水谷健一
    • Organizer
      第六回生命機能研究会
    • Place of Presentation
      龍谷大学梅田キャンパス
    • Year and Date
      2015-09-12
    • Related Report
      2015 Annual Research Report
  • [Presentation] Role of hypoxia and ROS during neocortical development2015

    • Author(s)
      Ken-ichi Mizutani
    • Organizer
      Neuro-Vascular Wiring International Symposium
    • Place of Presentation
      京都
    • Year and Date
      2015-01-28 – 2015-01-29
    • Related Report
      2014 Research-status Report
  • [Presentation] Prdm8 regulates the guidance molecules during neocortical development2014

    • Author(s)
      Ken-ichi Mizutani
    • Organizer
      Neuroscience 2014
    • Place of Presentation
      Washington DC
    • Year and Date
      2014-11-15
    • Related Report
      2014 Research-status Report
  • [Presentation] Role of hypoxic environment during neocortical development2014

    • Author(s)
      Aya Honda, Kazuyuki Yamagata, Mayuko Inoue, Mariko Komabayahi-Suzuki, Hiroshi Harada, and Ken-ichi Mizutani
    • Organizer
      Neuroscience 2014
    • Place of Presentation
      Washington DC
    • Year and Date
      2014-11-15
    • Related Report
      2014 Research-status Report
  • [Presentation] Angiogenesis in the developing neocortex2014

    • Author(s)
      Ken-ichi Mizutani
    • Organizer
      国際血管生物医学会
    • Place of Presentation
      京都
    • Year and Date
      2014-04-14
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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