Pathophysiolosical analysis of A2BP1, a candidate gene for ASD, in the brain development

2017 Fiscal Year Final Research Report

• Project/Area Number: 26860839
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Institute for Developmental Research, Aichi Human Service Center
• Principal Investigator: Hamada Nanako 愛知県心身障害者コロニー発達障害研究所, 神経制御学部, 特別研究員 (70721835)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: A2BP1 / ASD

Outline of Final Research Achievements

Gene abnormalities in A2BP1, encoding an mRNA-splicing factor, have been shown to cause autism spectrum disorder (ASD) and other neurodevelopmental disorders. We analyzed the relevance of A2BP1 during mouse corticogenesis with in vivo and in vitro methods. Knockdown of A2BP1 caused abnormal neuronal positioning in the cortex, which was attributed to impaired migration. Axon extension and dendritic arborization were also suppressed in A2BP1-deficient cortical neurons. In addition, electrophysiology experiments revealed significant defects in the membrane and synaptic properties of A2BP1-deficient neurons. This study shows that A2BP1 plays an important role in neuronal migration and synapse network formation during corticogenesis. Defects in these critical processes may induce structural and functional defects in cortical neurons, and consequently contribute to the emergence of the clinical symptoms of ASD and other neurodevelopmental disorders in patients with A2BP1 abnormalities.

Free Research Field

cortical development