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

• Project/Area Number: 25830030
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurophysiology / General neuroscience
• Research Institution: National 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: ¥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.

Research Products

• [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
  • Peer Reviewed / Open Access
• [Presentation] Analysis of the roles for the autism susceptibility candidate gene Auts2 in cerebellar development (2015)
  • 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
• [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
• [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
  • 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
  • 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