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Analysis of the role of autism susceptibility candidate gene Auts2 in brain development.

Research Project

Project/Area Number 25830030
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurophysiology / General neuroscience
Research InstitutionNational Center of Neurology and Psychiatry

Principal Investigator

HORI Kei  独立行政法人国立精神・神経医療研究センター, 神経研究所 代謝研究部, 室長 (70568790)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords自閉症 / 神経細胞移動 / 神経突起伸長 / 大脳皮質 / 細胞骨格 / 自閉症感受性遺伝子 / Rac1 / AUTS2 / アクチン細胞骨格 / 精神疾患
Outline of Final Research Achievements

Previous studies have demonstrated that the mutations in AUTS2 have been associated in multiple psychiatric disorders such as autism, intellectual disability and schizophrenia. In the CNS, Auts2 is highly expressed at several brain regions responsible for the higher brain functions such as frontal cortex, hippocampus and cerebellum. The physiological roles of AUTS2 in CNS development, however, remain unknown. Here we reveal the functions of AUTS2 in regulating cytoskeleton and neural development. In neurons, AUTS2 accumulates at the growth-cones, and activates Rac1 to promote the neurite-outgrowth. Loss-of-function experiments showed that AUTS2 participates in the neuronal migration and neuritogenesis in the cerebral cortex. Moreover, Auts2 KO mice displayed behavioral abnormalities including anxiety-related emotion and memory formation. Thus, our findings indicate that AUTS2 contributes to cortical development and is critical for the acquisition of neurocognitive function.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (6 results)

All 2015 2014 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (4 results) (of which Invited: 2 results) Remarks (1 results)

  • [Journal Article] Cytoskeletal regulation of AUTS2 in neuronal migration and neuritogenesis.2014

    • Author(s)
      Hori K., Nagai T., Shan W., Sakamoto A., Taya S., Hashimoto R., Hayashi T., Abe M., Yamazaki M., Nakao K., Nishioka T., Sakimura K., Yamada K., Kaibuchi K., Hoshino M.
    • Journal Title

      Cell Reports

      Volume: 9 Issue: 6 Pages: 2166-2179

    • DOI

      10.1016/j.celrep.2014.11.045

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Analysis of the roles for the autism susceptibility candidate gene Auts2 in cerebellar development2015

    • Author(s)
      Kei Hori, Ryo Aoki, Tomoo Owa, Miyashita Satoshi, Asami Sakamoto, Maya Yamazaki, Manabu Abe, Kenji Sakimura and Mikio Hoshino.
    • Organizer
      第8回神経発生討論会
    • Place of Presentation
      九州大学 病院キャンパス内 コラボステーションI
    • Year and Date
      2015-03-19 – 2015-03-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] 大脳皮質発生における新規自閉症感受性遺伝子の生理機能の解明2014

    • Author(s)
      Kei Hori, Taku Nagai, Wei Shan, Asami Sakamoto, Shinichiro Taya, Manabu Abe, Maya Yamazaki, Keiko Nakao, Tomoki Nishioka, Kenji Sakimura, Kiyofumi Yamada, Kozo Kaibuchi and Mikio Hoshino.
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜 展示ホール1階
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Analysis of the function of a psychiatric disorder-related gene during development.2014

    • Author(s)
      Mikio Hoshino, Kei Hori
    • Organizer
      国立精神・神経医療研究センター マックスプランク研究所 合同シンポジウム
    • Place of Presentation
      ザ・プリンス箱根 国際会議場
    • Year and Date
      2014-11-05 – 2014-11-07
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 精神疾患病態の解明に向けた新規自閉症感受性遺伝子Auts2の分子機能解析

    • Author(s)
      堀 啓
    • Organizer
      国立精神・神経医療研究センター 山梨大学 合同シンポジウム(山梨大学)
    • Place of Presentation
      山梨大学医学部
    • Related Report
      2013 Research-status Report
    • Invited
  • [Remarks] 自閉症、統合失調症、薬物依存など、 様々な精神疾患に関わる遺伝子の働きが初めて明らかに

    • URL

      http://www.ncnp.go.jp/press/press_release141219.html

    • Related Report
      2014 Annual Research Report

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

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