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COMPASS Family Histone Methyltransferase ASH2L Mediates Corticogenesis via Transcriptional Regulation of Wnt Signaling

ABSTRACT: This SuperSeries is composed of the SubSeries listed below Histone 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 shows fewer neurons that are also abnormal in composition and laminar position. Moreover, ASH2L loss impairs the 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 ASH2L is crucial for modulating Wnt signaling to maintain NPCs and generate a full complement of neurons during mammalian neocortex development.

ORGANISM(S): Mus musculus

PROVIDER: GSE120988 | GEO | 2019/07/16

REPOSITORIES: GEO

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