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Spatiotemporal control of microglial distribution in the developing cerebral cortex and its biological significance

Research Project

Project/Area Number 18K15003
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 48010:Anatomy-related
Research InstitutionNagoya University

Principal Investigator

Hattori Yuki  名古屋大学, 医学系研究科, 特任助教 (10754955)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsミクログリア / ニューロン / 脳発生 / ライブイメージング / CXCL12 / CXCR4 / 大脳 / 神経前駆細胞 / 二光子顕微鏡 / スライス培養 / 細胞移動 / CX3CR1 / 分布変化 / CXCL12/CXCR4
Outline of Final Research Achievements

Microglia change their distribution in a stage-dependent manner in the embryonic cerebral cortex. In mice, intrapallial microglial distribution is initially homogenous until embryonic day (E) 14, but these cells temporarily disappear from the cortical plate (CP) from E15 to E16. However, the mechanism and significance of this absence are unknown. We demonstrated that microglia bidirectionally migrate via attraction by CXCL12 released from the meninges and SVZ, and thereby exit the midembryonic CP. In addition, postmigratory neurons exposed to excessive microglia showed the disturbed expression pattern of genes implicated in functional neuronal maturation. Notably, this effect is primarily attributed to interleukin 6 and type I interferon secreted by microglia. These results suggest that "sanctuarization" from microglia in the midembryonic CP is required for neurons to appropriately fine-tune the expression of molecules needed for proper differentiation.

Academic Significance and Societal Importance of the Research Achievements

本研究により、正常脳におけるミクログリアの動態や神経系細胞との関わり合いについて理解が深まった。胎生期のみならず生後にわたる脳形成・成熟メカニズムの包括的な理解に貢献すると考えられる。一方で、母体の過剰な免疫活性化(感染症、肥満・低栄養状態)が、胎児の統合失調症、自閉症、ADHD等の発症リスクを高めることが報告されており、近年社会的にも母体炎症による胎児脳発生への影響について関心が高まっている。そこで発展的展望として、母体炎症に起因する脳発生の異常を未然に防ぐための予防法や治療法の画策など社会的ニーズに応じた研究展開も考えていきたい。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (22 results)

All 2020 2019 2018 Other

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (13 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results) Remarks (5 results)

  • [Journal Article] Transient microglial absence assists postmigratory cortical neurons in proper differentiation2020

    • Author(s)
      Yuki Hattori, Yu Naito, Yoji Tsugawa, Shigenori Nonaka, Hiroaki Wake, Takashi Nagasawa, Takaki Miyata
    • Journal Title

      Nature Communications

      Volume: 11 Issue: 1 Pages: 1631-1631

    • DOI

      10.1038/s41467-020-15409-3

    • NAID

      120006841707

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Two-photon microscopic observation of cell-production dynamics in the developing mammalian neocortex in utero2020

    • Author(s)
      Kawasoe, R, Shinoda, T, Hattori, Y, Nakagawam M, Quang Pham, T, Tanaka, Y, Sagou, K, Saito, K, Katsuki, S, Kotani, T, Sano, A, Fujimori, T, Miyata, T.
    • Journal Title

      Development, Growth & Differentiation

      Volume: 62 Issue: 2 Pages: 118-128

    • DOI

      10.1111/dgd.12648

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Embryonic neocortical microglia express Toll-like receptor 9 and respond to plasmid DNA injected into the ventricle: technical considerations regarding microglial distribution in electroporated brain walls.2018

    • Author(s)
      Hattori Y, Miyata T.
    • Journal Title

      eNeuro

      Volume: 5(6) Issue: 6 Pages: ENEURO.0312-18.2018

    • DOI

      10.1523/eneuro.0312-18.2018

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Microglia extensively survey the developing cortex via the CXCL12/CXCR4 system to help neural progenitors to acquire differentiated properties.2018

    • Author(s)
      Hattori Y, Miyata T.
    • Journal Title

      Genes to Cells

      Volume: 23(10) Issue: 10 Pages: 915-922

    • DOI

      10.1111/gtc.12632

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 胎生期大脳におけるミクログリア分布の時空間的制御とその生理学的意義2020

    • Author(s)
      服部祐季
    • Organizer
      第63回日本神経化学会大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 胎生期大脳におけるミクログリア分布の時空間的制御とその生理学的意義2020

    • Author(s)
      服部祐季
    • Organizer
      第10回名古屋大学医学系研究科・生理学研究所合同シンポジウム
    • Related Report
      2020 Annual Research Report
  • [Presentation] Microglial dynamics and its contribution to neurogenesis in mouse embryonic cerebral cortex2020

    • Author(s)
      服部祐季
    • Organizer
      第2回CIBoGリトリート
    • Related Report
      2020 Annual Research Report
  • [Presentation] 胎生期大脳におけるミクログリア動態とニューロン産生への貢献2020

    • Author(s)
      服部祐季
    • Organizer
      第14回神経発生討論会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 胎生期大脳におけるミクログリア動態とニューロン産生への貢献2020

    • Author(s)
      服部祐季
    • Organizer
      第126回日本解剖学会総会・全国学術集会 大会企画シンポジウム
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 胎生期大脳におけるミクログリア分布の時空間的制御とその生理学的意義2020

    • Author(s)
      服部祐季
    • Organizer
      第126回日本解剖学会総会・全国学術集会 日本解剖学会奨励賞受賞講演
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Transient absence of microglia underlies proper differentiation of the cortical plate2020

    • Author(s)
      Yuki Hattori
    • Organizer
      German-Japanese Developmental Neuroscience Meeting 2020
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 大脳原基皮質板におけるニューロン個性化完遂にはミクログリアの一時退出が必要である2019

    • Author(s)
      服部祐季、内藤裕、川口綾乃、宮田卓樹
    • Organizer
      NEURO2019(第42回日本神経科学大会・第62回日本神経化学会大会)
    • Related Report
      2019 Research-status Report
  • [Presentation] 胎生中期皮質板からのミクログリアの一時的な抜け出しは、ニューロンの適切な個性化獲得に必要である2019

    • Author(s)
      服部 祐季、内藤 裕、宮田 卓樹
    • Organizer
      第124回日本解剖学会総会・全国学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Spatiotemporally controlled microglial absence is required for cortical neuron subtype specification2019

    • Author(s)
      Yuki Hattori
    • Organizer
      第12回神経発生討論会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Spatiotemporally controlled microglial absence is required for cortical neuron subtype specification2019

    • Author(s)
      服部 祐季、内藤 裕、宮田 卓樹
    • Organizer
      第11回NAGOYAグローバルリトリート
    • Related Report
      2018 Research-status Report
  • [Presentation] Spatiotemporally controlled microglial absence is required for cortical neuron subtype specification2018

    • Author(s)
      服部 祐季、宮田 卓樹
    • Organizer
      第8回生理学研究所・名古屋大学大学院医学系研究科合同シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] 胎生期大脳におけるCXCL12/CXCR4を介したミクログリアの局在変化は神経前駆細胞の分化状態とニューロンの個性化を調節する2018

    • Author(s)
      服部 祐季、内藤 裕、宮田 卓樹
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Research-status Report
  • [Remarks] 胎生期大脳におけるミクログリアの分布調節機構とその意義

    • URL

      https://www.neurochemistry.jp/mu0czb0qu-15/

    • Related Report
      2020 Annual Research Report
  • [Remarks] プレスリリース「胎児の脳の不思議!~脳づくりが適切に進むよう,あえて"離れて見守る"ミクログリア~」

    • URL

      https://www.med.nagoya-u.ac.jp/medical_J/research/pdf/Nat_Com_200402.pdf

    • Related Report
      2019 Research-status Report
  • [Remarks] 脳内へのDNA注入により、免疫系細胞ミクログリアが異常な分布を示すことを発見

    • URL

      https://research-er.jp/articles/view/75356

    • Related Report
      2018 Research-status Report
  • [Remarks] IUE法による脳内への遺伝子導入でミクログリアが異常分布を示すことを発見-名大

    • URL

      http://www.qlifepro.com/news/20181121/microglia-abnormally-distributed-by-gene-transfer.html

    • Related Report
      2018 Research-status Report
  • [Remarks] eNeuro Blog Editor's picks

    • URL

      http://blog.eneuro.org/2019/01/editors-pick-1-jan

    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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