マウスにおけるクロマチンリモデリング因子BAF155はオリゴデンドロサイト-ニューロン間コミュニケーションを調整し、領域特異的なミエリン形成と自閉症様行動異常に関連する

Autism spectrum disorders (ASD) are neurodevelopmental disorders associated with synaptic deficits. Oligodendrocyte precursor cells (OPCs) are the only type of glial cells that establish direct synaptic connections with neurons within the central nervous system (CNS). However, the mechanism that results in the delicate construction of OPC-neuron synaptic connections remain poorly understood. Here we show in a mouse model that BAF155, a chromatin remodeling factor, is highly expressed in committed OPCs. BAF155 influences the OPC differentiation and myelination by coordinating the expression of multiple synapse-related genes that mediate OPC-neuron synaptic communication. The varying chromatin regulatory roles of BAF155 across brain regions give rise to local myelin deficits, contributing to the diverse clinical manifestations observed in individuals with ASD. Collectively, these results deepen our insight into OPC-neuron interactions under pathophysiological conditions and uncover a mechanism that integrates synaptic and ASD susceptibility genes, implying that abnormal OPC-neuron synaptogenesis could be an early instigator of ASD.