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Mechanism of neural circuit plasticity investigated from cell-type specific chromatin dynamics of juvenile brain

Research Project

Project/Area Number 16K14781
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Genetics/Chromosome dynamics
Research InstitutionNiigata University

Principal Investigator

SAKAI Akiko  新潟大学, 医歯学総合研究科, 日本学術振興会特別研究員 (70532745)

Research Collaborator NAKATO Ryuichiro  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords臨界期 / 抑制性ニューロン / PV細胞 / ChIP-seq / 細胞種特異的トランスクリプトーム / クロマチン / 転写制御 / Otx2 / トランスクリプトーム / パルブアルブミン / 精神疾患 / ミトコンドリア / 脳・神経 / 神経可塑性 / コヒーシン
Outline of Final Research Achievements

This study aimed to clarify gene expression and chromatin dynamics specific to interneurons (PV cells) that govern development of brain function depending on juvenile experience in mammals. Downstream target genes of Otx2 homeoprotein necessary for development of PV cells were identified comprehensively using ChIP-seq and interneuron-specific RNA-seq. Important functions of Otx2 were suggested to be promoting functional development for fast-spiking property characteristic to PV cells as well as homeostatic regulation. Moreover, functional analysis of a cohesin-related factor indicated importance of regulating chromatin structure in maturation of PV cells.

Academic Significance and Societal Importance of the Research Achievements

脳の成長には、神経回路の興奮性を調節する抑制性の神経細胞の働きが不可欠である。本研究では、経験に応じて脳の発達を促すOtx2が調節し得る遺伝子として、抑制性神経細胞の機能に必要な遺伝子群や、細胞の恒常性を保つ抗酸化遺伝子を新たに発見した。また、遺伝子調節の背景にある染色体の構造の調節の重要性も見出した。本研究の成果は、脳の成長のしくみと、その異常による精神疾患の原因の解明につながると期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (11 results)

All 2019 2018 2017

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (7 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Experience-dependent transcriptional regulation in juvenile brain development2018

    • Author(s)
      Sakai Akiko、Sugiyama Sayaka
    • Journal Title

      Development, Growth & Differentiation

      Volume: 60 Issue: 8 Pages: 473-482

    • DOI

      10.1111/dgd.12571

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 特集 大脳皮質-成り立ちから機能へ 臨界期の機構─子どもの脳の柔軟性を紐解く2017

    • Author(s)
      酒井 晶子、杉山 清佳
    • Journal Title

      生体の科学

      Volume: 68 Issue: 1 Pages: 54-58

    • DOI

      10.11477/mf.2425200575

    • ISSN
      0370-9531, 1883-5503
    • Year and Date
      2017-02-15
    • Related Report
      2016 Research-status Report
  • [Journal Article] Genome-Wide Target Analyses of Otx2 Homeoprotein in Postnatal Cortex2017

    • Author(s)
      Sakai Akiko、Nakato Ryuichiro、Ling Yiwei、Hou Xubin、Hara Norikazu、Iijima Tomoya、Yanagawa Yuchio、Kuwano Ryozo、Okuda Shujiro、Shirahige Katsuhiko、Sugiyama Sayaka
    • Journal Title

      Frontiers in Neuroscience

      Volume: 11 Pages: 307-307

    • DOI

      10.3389/fnins.2017.00307

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chondroitin Sulfate Is Required for Onset and Offset of Critical Period Plasticity in Visual Cortex2017

    • Author(s)
      Hou X, Yoshioka N, Tsukano H, Sakai A, Miyata S, Watanabe Y, Yanagawa Y, Sakimura K, Takeuchi K, Kitagawa H, Hensch TK, Shibuki K, Igarashi M, Sugiyama S
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 12646-12646

    • DOI

      10.1038/s41598-017-04007-x

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Regulation of transcription and chromatin structure in postnatal cortical development2019

    • Author(s)
      Akiko Sakai
    • Organizer
      The 9th BRI International Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 経験による脳の発達に必須な抑制性介在ニューロンにおける転写制御2018

    • Author(s)
      酒井 晶子・中戸 隆一郎・凌 一葦・侯 旭濱・飯島 友也・原 範和・桑野 良三・奥田 修二郎・白髭 克彦・杉山 清佳
    • Organizer
      第41回日本分子生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Analysis of chromatin dynamics in postnatal cortical plasticity2018

    • Author(s)
      Akiko Sakai
    • Organizer
      Brain Research Institute the 8th international symposium
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Genome-wide targets of Otx2 homeoprotein in postnatal cortical interneuron are implicated in mitochondria and neurodevelopmental disorders /発達期の抑制性介在ニューロンにおけるOtx2下流因子群はミトコンドリア機能と精神疾患に関わる2017

    • Author(s)
      酒井 晶子、中戸 隆一郎、凌 一葦、侯 旭濱、原 範和、飯島 友也、柳川 右千夫、桑野 良三、奥田 修二郎、白髭 克彦 、杉山 清佳
    • Organizer
      第10回神経発生討論会
    • Place of Presentation
      秋保リゾートホテルクレセント(宮城県仙台市)
    • Year and Date
      2017-03-10
    • Related Report
      2016 Research-status Report
  • [Presentation] 生後の抑制性介在ニューロン発達におけるホメオタンパク質Otx2の網羅的ターゲット解析2017

    • Author(s)
      酒井 晶子、中戸 隆一郎、凌 一葦、侯 旭濱、飯島 友也、原 範和、柳川 右千夫、桑野 良三、奥田 修二郎、白髭 克彦、杉山 清佳
    • Organizer
      第11回日本エピジェネティクス研究会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] 発達期の抑制性介在ニューロンにおけるOtx2下流因子群は代謝と精神疾患に関わる2017

    • Author(s)
      酒井 晶子、中戸 隆一郎、凌 一葦、侯 旭濱、飯島 友也、原 範和、柳川 右千夫、桑野 良三、奥田 修二郎、白髭 克彦、杉山 清佳
    • Organizer
      第58回新潟生化学懇話会
    • Related Report
      2017 Research-status Report
  • [Presentation] Genome-wide Target Analyses of Otx2 Homeoprotein In Postnatal Cortical Interneuron2017

    • Author(s)
      Sakai, A., Nakato, R., Ling, Y., Hou, X., Hara, N., Iijima, T., Yanagawa, Y., Kuwano, R., Okuda, S., Shirahige, K., Sugiyama, S.
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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