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Molecular mechanisms underlying neuronal migration during neocortical development

Research Project

Project/Area Number 25440114
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Developmental biology
Research InstitutionKeio University

Principal Investigator

Hirota Yuki  慶應義塾大学, 医学部(信濃町), 講師 (00453548)

Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords大脳皮質 / 層構造 / ニューロン移動 / リーリンシグナル / リーリン / ApoER2 / VLDLR / 脳室下帯
Outline of Final Research Achievements

The extracellular protein Reelin sends signals to various downstream molecules by binding to its receptors, ApoER2 and VLDLR and exerts essential roles in the formation of the mammalian layered neocortex. Here, we we found that the neurons ectopically invaded the MZ and that neuronal migration was disrupted in the intermediate zone in the Apoer2 KO mice. Expression of ApoER2 partially but significantly rescued Apoer2 KO phenotype, suggesting that ApoER2 control migratory behavior of neurons by both cell-autonomous and non-cell-autonomous manners. As for cell-autonomous functions, we found that Rap1/integrin α5 and Akt restored the failure of termination of migration beneath the MZ and neuronal migration in the IZ of Apoer2 KO mice. These data indicate that ApoER2 controls multiple processes in neuronal migration, including the early stage of radial migration and termination of migration beneath the MZ in the developing cerebral cortex.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (11 results)

All 2017 2016 2015 2014 2013

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (7 results)

  • [Journal Article] ApoER2 controls not only neuronal migration in the intermediate zone, but also termination of migration in the developing cerebral cortex.2017

    • Author(s)
      Yuki Hirota, Ken-ichiro Kubo, Takahiro Fujino, Tokuo T. Yamamoto, and Kazunori Nakajima
    • Journal Title

      Cerebral Cortex

      Volume: in press Issue: 1 Pages: 223-235

    • DOI

      10.1093/cercor/bhw369

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Roles of Wnt signaling in the neurogenic niche of the adult mouse ventricular-subventricular zone2016

    • Author(s)
      Hirota Y, Sawada M, Huang SH, Ogino T, Ohata S, Kubo A, Sawamoto K
    • Journal Title

      Neurochemical Research

      Volume: 41 Issue: 1-2 Pages: 222-230

    • DOI

      10.1007/s11064-015-1766-z

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Reelin has a preventive effect on phencyclidine-induced cognitive and sensory-motor gating deficits2015

    • Author(s)
      Kazuhiro Ishii, Taku Nagai, Yuki Hirota, Mariko Noda, Toshitaka Nabeshima, Kiyofumi Yamada, Ken-ichiro Kubo, and Kazunori Nakajima
    • Journal Title

      Neurosci. Res.

      Volume: 印刷中 Pages: 30-36

    • DOI

      10.1016/j.neures.2014.12.013

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Reelin receptors ApoER2 and VLDLR are expressed in distinct spatio-temporal patterns in developing mouse cerebral cortex.2014

    • Author(s)
      Hirota Y, Kubo K, Katayama K, Honda T, Fujino T, Yamamoto TT and Nakajima K
    • Journal Title

      J. Comp. Neurol

      Volume: 523(3) Issue: 3 Pages: 463-78

    • DOI

      10.1002/cne.23691

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] リーリン受容体ApoER2による大脳皮質ニューロン移動と停止の制御機構2017

    • Author(s)
      廣田ゆき、久保健一郎、藤野貴広、山本徳男、仲嶋一範
    • Organizer
      第122回日本解剖学会総会・全国学術集会
    • Place of Presentation
      長崎大学(長崎県長崎市)
    • Year and Date
      2017-03-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] ApoER2 controls not only neuronal migration but also termination of migration in the developing cerebral cortex2016

    • Author(s)
      廣田ゆき、久保健一郎、藤野貴広、山本徳男、仲嶋一範
    • Organizer
      第121回日本解剖学会総会・全国学術集会
    • Place of Presentation
      ビッグパレットふくしま ( 福島県郡山市)
    • Year and Date
      2016-03-30
    • Related Report
      2015 Research-status Report
  • [Presentation] Roles of ApoER2 in neuronal migration and termination of migration in the developing cerebral cortex2016

    • Author(s)
      Yuki Hirota, Ken-ichiro Kubo, Takahiro Fujino, Tokuo T. Yamamoto, and Kazunori Nakajima
    • Organizer
      第39回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] リーリン受容体ApoER2とVLDLRの大脳皮質形成過程における発現と機能2014

    • Author(s)
      廣田ゆき、久保健一郎、 本田岳夫、藤野貴広、山本徳男、仲嶋一範
    • Organizer
      第36回日本生物学的精神医学会・第57回日本神経化学会大会合同年会
    • Place of Presentation
      奈良県文化会館・奈良県新公会堂
    • Year and Date
      2014-09-30
    • Related Report
      2014 Research-status Report
  • [Presentation] Regulation of migratory behavior of excitatory neurons by the Reelin signaling via its receptors2013

    • Author(s)
      Yuki Hirota, Ken-ichiro Kubo, and Kazunori Nakajima
    • Organizer
      24th Biennial International Society for Neurochemistry (ISN) Meeting
    • Place of Presentation
      Cancun, Mexico
    • Related Report
      2013 Research-status Report
  • [Presentation] Function of Reelin Signaling via its Receptor in Migrating Neurons in Developing Cerebral Cortex2013

    • Author(s)
      Yuki Hirota, Ken-ichiro Kubo, Kazunori Nakajima
    • Organizer
      The 25th CDB Meeting “Cilia and Centrosomes, from Fertilization to Cancer”
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report
  • [Presentation] リーリンシグナルは受容体を介して神経細胞移動を制御する2013

    • Author(s)
      廣田ゆき、久保健一郎、仲嶋一範
    • Organizer
      第36回日本神経科学大会・第56回日本神経化学会大会・第23回日本神経回路学会大会合同大会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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