Chromatin Regulation by BAF170 Controls Cerebral Cortical Size and Thickness
Open accessAbstract
Increased cortical size is essential to the enhanced intellectual capacity of primates during mammalian evolution. The mechanisms that control cortical size are largely unknown. Here, we show that mammalian BAF170, a subunit of the chromatin remodeling complex mSWI/SNF, is an intrinsic factor that controls cortical size. We find that conditional deletion of BAF170 promotes indirect neurogenesis by increasing the pool of intermediate progenitors (IPs) and results in an enlarged cortex, whereas cortex-specific BAF170 overexpression results in the opposite phenotype. Mechanistically, BAF170 competes with BAF155 subunit in the BAF complex, affecting euchromatin structure and thereby modulating the binding efficiency of the Pax6/REST-corepressor complex to Pax6 target genes that regulate the generation of IPs and late cortical progenitors. Our findings reveal a molecular mechanism mediated by the mSWI/SNF chromatin-remodeling complex that controls cortical architecture.
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SMARCC2 encodes a subunit of the chromatin remodeling complex mSWI/SNF that directly controls neurogenesis in the developing cerebral cortex by regulating its size and thickness.
“Interestingly, one positively selected site was also detected in SMARCC2, which encodes a subunit of the chromatin remodeling complex mSWI/SNF that directly controls neurogenesis in the developing cerebral cortex by regulating its size and thickness44.”
From Distinct selective forces and Neanderthal introgression shaped genetic diversity at genes involved in neurodevelopmental disorders (2017) · cites this paper as [44]
The Abstract and Discussion identify BAF170 as an mSWI/SNF subunit that controls cortical neurogenesis, with consequences for cortical size and thickness. Our copy does not identify BAF170 as the product of SMARCC2, and it describes neurogenesis as affecting cortical dimensions rather than being controlled by them. (LLM, conf=0.84)
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- Authors
- Tuoc, T. C., Boretius, S., Sansom, S. N., Pitulescu, M.-E., Frahm, J., Livesey, F. J., & Stoykova, A.
- Affiliations
- Nanoscale Microscopy and Molecular Physiology of the Brain Cluster of Excellence 171 — DFG Research Center 103 (DE)
- University of Cambridge (GB)
- Max Planck Institute for Biophysical Chemistry (DE)
- Corresponding author
- Stoykova, Anastassia
- ORCID
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 25
- Issue
- 3
- Pages
- 256-269
- ISSN
- 1534-5807 (ISSN-L)
- OpenAlex
- W2039033194
- Cited by
- 177
- References
- 41
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 15 · 2023: 14 · 2022: 11 · 2021: 18 · 2020: 11 · 2019: 17 · 2018: 18 · 2017: 9 · 2016: 16 · 2015: 15 · 2014: 14 · 2013: 7
- FWCI
- 6.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- GRO (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (092096)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- BAF170, BAF155, cortical thickness, intermediate progenitor cells, Pax6, cortical progenitors, conditional gene deletion, primate brain evolution
- MeSH terms
- PAX6 Transcription Factor, RE1-Silencing Transcription Factor, Animals, Cerebral Cortex, Chromatin, Eye Proteins, Female, HeLa Cells, Histones, Humans, Male, Mice, Transgenic, Neurons, Nuclear Proteins, Organ Size, Promoter Regions, Genetic, Protein Binding, Repressor Proteins, Transcription Factors, Homeodomain Proteins, DNA Methylation, Protein Interaction Mapping, Chromatin Assembly and Disassembly, Epigenesis, Genetic, Multiprotein Complexes, Mice, Paired Box Transcription Factors, Neurogenesis
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