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

2014 Fiscal Year Final Research Report

• 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
• Keywords: 自閉症 / 神経細胞移動 / 神経突起伸長 / 大脳皮質 / 細胞骨格

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.

Free Research Field

神経科学