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A novel gene-environment interface: neuroepitranscriptomics

Publicly Offered Research

Project AreaIntegrative research toward elucidation of generative brain systems for individuality
Project/Area Number 19H04907
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Complex systems
Research InstitutionInstitute of Physical and Chemical Research (2020)
Kyoto University (2019)

Principal Investigator

王 丹  国立研究開発法人理化学研究所, 生命機能科学研究センター, チームリーダー (50615482)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2020: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Keywords環境 / 行動 / エピトランスクリプトーム / RNA修飾 / シナプトーム / 個性 / エンリッチ / 孤立飼育 / 行動解析
Outline of Research at the Start

多様性と柔軟性に富んだエピトランスクリプトームが遺伝と環境が働き合う分子基盤として、高い時空間分解能をもち、環境適応の過程から生まれる個性創発に適することを示している。本研究はこの可能性を検証するために、2種類のマウス系統(BALB/cとC57Bl/6)の環境変化に対する適応能力の差に注目して、それぞれのマウスの環境変化に対するm6A応答性を測定する。さらに、m6A制御経路を撹乱したC57Bl/6マウスを用い、「環境変化適応性」と「活動依存的シナプス多様性」を測定し、動的なRNA修飾を介した「遺伝-環境」相互作用の新規分子脳科学的基盤を明らかにする。

Outline of Annual Research Achievements

本研究は、多様性と柔軟性に富んだエピトランスクリプトームが遺伝と環境が働き合う分子基盤として、高い時空間分解能をもち、環境適応の過程から生まれる個性創発に適することに注目して、2種類のマウス系統(BALB/cとC57Bl/6)の環境変化に対する適応能力とm6A制御経路を撹乱したC57Bl/6マウスを用い、「環境変化適応性」と「活動依存的シナプス多様性」を測定した。動的なRNA修飾を介した「遺伝-環境」相互作用の新規分子脳科学的基盤の一端を明らかにした。
具体的には、思春期BALB/cの8週間にわたる飼育環境の制御(環境エンリッチ、スタンダード、社会隔離)を行ったあとに、マウスのさまざまな生理的機能および行動機能(感覚、運動、認知、記憶など)を測定した。さらに、「豊か」な環境から「通常」の環境への急激な環境落差を経験したマウス集団内では、突然の激しい攻撃行動・昼夜の活動リズムの乱れ・個体間平均距離の増加が起きることを発見し、報告した(Sukegawa et al., 2022)。さらに、このような環境操作に対する動物の行動的応答は、系統差がある上に、m6A制御経路を撹乱したC57Bl/6マウスにおいても個体差が観察された。この知見は、個性を創発する新規の分子脳科学的基盤をm6A修飾の理解を端緒として、バイオロジカルなエビデンスを示した。さらに、侵襲的介入が可能な動物モデルを用いて、遺伝子改変および環境変化下の集団の行動の変容を示し、その遺伝-環境相互作用の基盤の一端を明らかにする第一歩を踏み出した結果となった(Wang DO, Semin. Cell Dev. Biol., (2021)。

Research Progress Status

令和2年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和2年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (21 results)

All 2022 2021 2019 Other

All Int'l Joint Research (1 results) Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Open Access: 2 results,  Peer Reviewed: 1 results) Presentation (16 results) (of which Int'l Joint Research: 15 results,  Invited: 11 results)

  • [Int'l Joint Research] The Florey Institute(オーストラリア)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Long-lasting housing environment manipulation and acute loss of environmental enrichment impact BALB/c mice behaviour in multiple functional domains2022

    • Author(s)
      Sukegawa, M., Yoshihara, T., Hou, S., Asano, M., Hannan., AJ. and Wang, DO.
    • Journal Title

      European Journal of Neuroscience

      Volume: 55 Issue: 5 Pages: 1118-1140

    • DOI

      10.1111/ejn.15602

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Epitranscriptomic regulation of cognitive development and decline2021

    • Author(s)
      Wang Dan Ohtan
    • Journal Title

      Seminars in Cell & Developmental Biology

      Volume: 0 Pages: 0-0

    • DOI

      10.1016/j.semcdb.2021.11.019

    • Related Report
      2020 Annual Research Report
    • Open Access
  • [Journal Article] Nanoparticle-based local translation reveals mRNA as translation-coupled scaffold with anchoring function2019

    • Author(s)
      Kashida S, Wang DO, Saito H, Gueroui Z*
    • Journal Title

      PNAS

      Volume: 116(27) Pages: 13346-13351

    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Journal Article] RNA 化学修飾と精神疾患-神経シナプスからの理解2019

    • Author(s)
      助川桃枝・王 丹*
    • Journal Title

      医学の歩み

      Volume: 269(10) Pages: 811-812

    • Related Report
      2019 Annual Research Report
  • [Presentation] 神経シナプス構造とN6-メチルアデノシンRNA修飾2022

    • Author(s)
      Dan Ohtan Wang
    • Organizer
      127th Annual Meeting of the Japanese Association of Anatomists
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Synaptic Epitranscriptomics2021

    • Author(s)
      Dan Ohtan Wang
    • Organizer
      The 44th Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Schizophrenia and autism-associated mutations and disrupted m6A signal by YTHDF1 causes defects in microtubule function and neurodevelopment2021

    • Author(s)
      Rohini Roy
    • Organizer
      The 44th Annual Meeting of the Molecular Biology Society of Japan
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Emergence of severe aggression from acute environmental de-enrichment in mice2021

    • Author(s)
      Sukegawa Momoe
    • Organizer
      RIKEN BDR Symposium 2022 "Emergence in Biological Systems: Challenges to Bridging Hierarchies"
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 周囲環境ならびに急激な環境変化がマウス行動に及ぼす影響2021

    • Author(s)
      助川 桃枝
    • Organizer
      日本心理学会第85回大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] To dissect behavioral impact of environmental factors on BALB/c mice2021

    • Author(s)
      Sukegawa Momoe
    • Organizer
      The 80th Fujihara Seminar "Molecular and cellular mechanisms of brain systems generating individuality"
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] tion Effects of enriched environment, social isolation, and enrichment removal on BALB/c mice behaviors2021

    • Author(s)
      Sukegawa Momoe
    • Organizer
      第44回日本神経科学大会・第1回CJK 国際会議
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] tion Function of m6A reader YTHDF1 in excitatory neurons: a molecular and behavioral analysis of YTHDF1 conditional knockout mice2021

    • Author(s)
      Hou Shengqun
    • Organizer
      The 44th Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Emerging Epitranscriptomics in the Synapses2019

    • Author(s)
      Wang DO et al
    • Organizer
      Indian Academy of Neuroscience
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Emerging Neuropitranscriptomics2019

    • Author(s)
      Wang DO et al
    • Organizer
      2019 Tzu Chi-Academia Sinica Biomedical Conference
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Dynamic RNA Imaging2019

    • Author(s)
      Wang DO et al
    • Organizer
      Australasian Neuroscience Society meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] RNA Epigenetics in Neurons and Synapses2019

    • Author(s)
      Wang DO
    • Organizer
      生理研研究会「記憶研究会」
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Synaptic Epitranscriptomics and Dynamic RNA imaging2019

    • Author(s)
      Wang DO et al
    • Organizer
      EBPS Biennial Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] RNA modifications and translational regulation at neuronal synapses2019

    • Author(s)
      Wang DO et al
    • Organizer
      ISN-ASN
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Epitranscriptomics in Synapses2019

    • Author(s)
      Wang DO et al
    • Organizer
      NEURO2019, Asian Chemical Biology Initiative 2019 Yangon Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Emerging Neuropitranscriptomics2019

    • Author(s)
      Wang DO et al
    • Organizer
      2nd SPIRITS International Symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2019-04-18   Modified: 2022-12-28  

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