Epigenetic Regulation by BAF Complexes Limits Neural Stem Cell Proliferation by Suppressing Wnt Signaling in Late Embryonic Development

Stem Cell Reports
Huong NguyenTran Tuoc

Abstract

During early cortical development, neural stem cells (NSCs) divide symmetrically to expand the progenitor pool, whereas, in later stages, NSCs divide asymmetrically to self-renew and produce other cell types. The timely switch from such proliferative to differentiative division critically determines progenitor and neuron numbers. However, the mechanisms that limit proliferative division in late cortical development are not fully understood. Here, we show that the BAF (mSWI/SNF) complexes restrict proliferative competence and promote neuronal differentiation in late corticogenesis. Inactivation of BAF complexes leads to H3K27me3-linked silencing of neuronal differentiation-related genes, with concurrent H3K4me2-mediated activation of proliferation-associated genes via de-repression of Wnt signaling. Notably, the deletion of BAF complexes increased proliferation of neuroepithelial cell-like NSCs, impaired neuronal differentiation, and exerted a Wnt-dependent effect on neocortical and hippocampal development. Thus, these results demonstrate that BAF complexes act as both activators and repressors to control global epigenetic and gene expression programs in late corticogenesis.

Citations

Apr 4, 2020·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Juanmei GaoWanhua Shen
Jul 10, 2019·Experimental and Therapeutic Medicine·Ka WangShiyuan Xu
Apr 26, 2019·Annals of Clinical and Translational Neurology·Milka PringsheimKnut Brockmann
Aug 9, 2020·Human Molecular Genetics·Ummi Ciptasari, Hans van Bokhoven
Dec 3, 2020·Cellular and Molecular Life Sciences : CMLS·Britt MossinkNael Nadif Kasri
Jan 8, 2021·Current Opinion in Neurobiology·Jérôme Bonnefont, Pierre Vanderhaeghen
Nov 6, 2020·Scientific Reports·Anna FliednerChristiane Zweier
Jun 8, 2021·Frontiers in Cell and Developmental Biology·Godwin SokporTran Tuoc

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Datasets Mentioned

BETA
GSE37151

Methods Mentioned

BETA
co-immunoprecipitation
RNA-seq
immunoprecipitation
ChIP-seq
Transgenic
fluorescence microscopy

Software Mentioned

Neurolucida
ImageJ

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