Department of Developmental Neuroscience, United Center for Advanced Research and Translational Medicine (ART), Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Department of Histology and Neuroanatomy, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.
Brain Res. 2019 Feb 15;1705:95-103. doi: 10.1016/j.brainres.2018.02.041. Epub 2018 Feb 27.
Pax6 transcription factor is a key player in several aspects of brain development and function. Autism spectrum disorder (ASD) is a neurodevelopmental disorder in which several loci and/or genes have been suggested as causative candidate factors. Based on data obtained from meta-analyses of the transcriptome and ChIP analyses, we hypothesized that the neurodevelopmental gene PAX6 regulates and/or binds to a large number of genes (including many ASD-related ones) that modulate the fate of neural stem/progenitor cells and functions of neuronal cells, subsequently affecting animal behavior. Network analyses of PAX6/ASD-related molecules revealed significant clusters of molecular interactions involving regulation of cell-cell adhesion, ion transport, and transcriptional regulation. We discuss a novel function of Pax6 as a chromatin modulator that alters the chromatin status of ASD genes, thereby inducing diverse phenotypes of ASD and related neurodevelopmental diseases.
Pax6 转录因子是大脑发育和功能的几个方面的关键参与者。自闭症谱系障碍（ASD）是一种神经发育障碍，其中有几个基因座和/或基因被认为是致病候选因素。基于对转录组和 ChIP 分析的荟萃分析获得的数据，我们假设神经发育基因 PAX6 调节和/或结合到大量基因（包括许多与 ASD 相关的基因），这些基因调节神经干细胞/祖细胞的命运和神经元细胞的功能，进而影响动物行为。PAX6/ASD 相关分子的网络分析显示涉及细胞间粘附、离子转运和转录调控的分子相互作用的显著簇。我们讨论了 Pax6 作为染色质调节剂的新功能，该功能改变了 ASD 基因的染色质状态，从而诱导 ASD 和相关神经发育疾病的多种表型。
