Analysis of the AUTS2 gene and its relationship with focal cortical dysplasia

• Project/Area Number: 15K14337
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: Hoshino Mikio 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 病態生化学研究部, 部長 (70301273)
• Project Period (FY): 2015-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
• Keywords: 神経科学 / 発生・分化 / 脳神経疾患 / 脳・神経 / 解剖学

Outline of Final Research Achievements

AUTS2 is related to various psychiatric disorders, but its function has been elusive. We have previously found that AUTS2 activates Rac1 and simultaneously downregulates Cdc42 to reorganize actin cytoskeleton and is involved in cortical neuronal migration and neuritogenesis.In this study, we further found that AUTS2 is also involved in synaptogenesis in the developing brain. Moreover, Auts2-deficient mice display behavioral abnormalities including anxiety-related emotion and memory formation. These findings suggest that AUTS2 acts as a novel regulator for Rho family GTPases contributing to brain development and give good insights into the pathology of human psychiatric disorders with AUTS2 mutations.

Research Products

• [Journal Article] Origins of oligodendrocytes in the cerebellum, whose development is controlled by the transcription factor, Sox9 (2016)
  • Author(s): Hashimoto R, Hori K, Owa T, Miyashita S, Dewa K, Masuyama N, Sakai K, Hayase Y, Seto Y, Inoue YU, Inoue T, Ichinohe N, Kawaguchi Y, Akiyama H, Koizumi S, Hoshino M
  • Journal Title: Mech Dev Volume: 140 Pages: 25-40
  • DOI: 10.1016/j.mod.2016.02.004
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Heterozygous Disruption of Autism susceptibility candidate 2 Causes Impaired Emotional Control and Cognitive Memory. (2015)
  • Author(s): Hori K, Nagai T, Shan W, Sakamoto A, Abe M, Yamazaki M, Sakimura K, Yamada K, Hoshino M.
  • Journal Title: PLoS One Volume: 30 Issue: 12 Pages: e0145979-e0145979
  • DOI: 10.1371/journal.pone.0145979
  • Peer Reviewed / Open Access
• [Journal Article] Classic cadherin expressions balance postnatal neuronal positioning and dendrite dynamics to elaborate the specific cytoarchitecture of the mouse cortical area (2015)
  • Author(s): Egusa SF, Inoue YU, Asami J, Terakawa YW, Hoshino M, Inoue T
  • Journal Title: Neurosci Res Volume: 105 Pages: 49-64
  • DOI: 10.1016/j.neures.2015.09.006
  • Peer Reviewed
• [Presentation] Cytoplasmic function of AUTS2 in neural network formation (2015)
  • Author(s): Hoshino M, Nagai T, Shen W, Sakamoto A, Taya S, Hashimoto R, Hayashi T, Abe M, Yamazaki M, Nakao K, Nishioka T, Sakimura K, Yamada K, Kaibuchi K, Hori K
  • Organizer: Society for Neuroscience 45th annual meeting
  • Place of Presentation: McCormick Place, Chicago, IL, USA
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] Analysis of autism susceptibility candidate 2 gene during development (2015)
  • Author(s): Hoshino M, Hori K
  • Organizer: Tohoku Forum for Creativity, Frontiers of Brain Science, “Development and Disease” symposium
  • Place of Presentation: Tohoku University, Sendai, Japan
  • Year and Date: 2015-08-24
  • Int'l Joint Research / Invited
• [Presentation] 各種精神疾患とAUTS2遺伝子、そしてヒトの進化 (2015)
  • Author(s): 星野幹雄
  • Organizer: 平成27年度生理学研究所研究会「シナプスの構造構築と機能発現の分子基盤」
  • Place of Presentation: 生理学研究所, 岡崎
  • Year and Date: 2015-06-18
  • Invited
• [Presentation] Physiological and pathological analyses of an autism-related gene (2015)
  • Author(s): Hoshino M
  • Organizer: EMBO Workshop on Cortical Development in Health and Disease
  • Place of Presentation: Weizmann Institute of Science, Rehovot, Israel
  • Year and Date: 2015-04-26
  • Int'l Joint Research / Invited