The COMPASS Family Protein ASH2L Mediates Corticogenesis via Transcriptional Regulation of Wnt Signaling

Publication date: 16 July 2019Source: Cell Reports, Volume 28, Issue 3Author(s): Liang Li, Xiangbin Ruan, Chang Wen, Pan Chen, Wei Liu, Liyuan Zhu, Pan Xiang, Xiaoling Zhang, Qunfang Wei, Lin Hou, Bin Yin, Jiangang Yuan, Boqin Qiang, Pengcheng Shu, Xiaozhong PengSummaryHistone methylation is essential for regulating gene expression during organogenesis to maintain stem cells and execute a proper differentiation program for their descendants. Here we show that the COMPASS family histone methyltransferase co-factor ASH2L is required for maintaining neural progenitor cells (NPCs) and the production and positioning of projection neurons during neocortex development. Specifically, loss of Ash2l in NPCs results in malformation of the neocortex; the mutant neocortex has fewer neurons, which are also abnormal in composition and laminar position. Moreover, ASH2L loss impairs trimethylation of H3K4 and the transcriptional machinery specific for Wnt-β-catenin signaling, inhibiting the proliferation ability of NPCs at late stages of neurogenesis by disrupting S phase entry to inhibit cell cycle progression. Overexpressing β-catenin after ASH2L elimination rescues the proliferation deficiency. Therefore, our findings demonstrate that ASH2L is crucial for modulating Wnt signaling to maintain NPCs and generate a full complement of neurons during mammalian neocortex development.Graphical Abstract

Source: Cell Reports - July 17, 2019 Category: Cytology Source Type: research