Stem Cell Reports
Volume 10, Issue 6, 5 June 2018, Pages 1734-1750
open access
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Epigenetic Regulation by BAF Complexes Limits Neural Stem Cell Proliferation by Suppressing Wnt Signaling in Late Embryonic Development

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Loss of BAF complexes increases H3K27me3 and H3K4me2 marks in late corticogenesis

BAF complexes epigenetically regulate neural proliferation and differentiation

BAF complexes suppress neuroepithelial cell fate and Wnt signaling

BAF complexes control cortical development in a Wnt signaling-dependent manner


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.


cortical development
hippocampal development
neural stem cells
chromatin remodeling
BAF (mSWI/SNF) complexes

Present address: Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston MA 02115, USA


Co-first author