Abstract
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.
Copyright © 2013 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cerebral Cortex / metabolism*
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Cerebral Cortex / pathology
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Chromatin / genetics
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Chromatin / metabolism*
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Chromatin Assembly and Disassembly
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DNA Methylation
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Epigenesis, Genetic
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Eye Proteins / genetics
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Eye Proteins / metabolism
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Female
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HeLa Cells
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Histones / genetics
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Histones / metabolism
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Humans
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Male
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Mice
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Mice, Transgenic / genetics
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Mice, Transgenic / metabolism
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Multiprotein Complexes / genetics
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Multiprotein Complexes / metabolism
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Neurogenesis*
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Neurons / metabolism
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Organ Size
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PAX6 Transcription Factor
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Paired Box Transcription Factors / genetics
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Paired Box Transcription Factors / metabolism
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Promoter Regions, Genetic
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Protein Binding
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Protein Interaction Mapping
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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Chromatin
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Cux1 protein, mouse
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Eye Proteins
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Histones
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Homeodomain Proteins
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Multiprotein Complexes
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Nuclear Proteins
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PAX6 Transcription Factor
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PAX6 protein, human
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Paired Box Transcription Factors
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Pax6 protein, mouse
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RE1-silencing transcription factor
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Repressor Proteins
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Smarcc1 protein, mouse
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Transcription Factors