title: Snf2l regulates Foxg1-dependent progenitor cell expansion in the developing brain.
abstract: Balancing progenitor cell self-renewal and differentiation is essential for brain development and is regulated by the activity of chromatin remodeling complexes. Nevertheless, linking chromatin changes to specific pathways that control cortical histogenesis remains a challenge. Here we identify a genetic interaction between the chromatin remodeler Snf2l and Foxg1, a key regulator of neurogenesis. Snf2l mutant mice exhibit forebrain hypercellularity arising from increased Foxg1 expression, increased progenitor cell expansion, and delayed differentiation. We demonstrate that Snf2l binds to the Foxg1 locus at midneurogenesis and that the phenotype is rescued by reducing Foxg1 dosage, thus revealing that Snf2l and Foxg1 function antagonistically to regulate brain size.
authors.affiliation: Regenerative Medicine Program, Ottawa Hospital Research Institute, and Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Yip
authors.forename: Chelsea P
authors.initials: CP
authors.lastname: Corcoran
authors.forename: Matías
authors.initials: M
authors.lastname: Alvarez-Saavedra
authors.forename: Adriana
authors.initials: A
authors.lastname: DeMaria
authors.forename: Stephen
authors.initials: S
authors.lastname: Rennick
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Mears
authors.forename: Michael A
authors.initials: MA
authors.lastname: Rudnicki
authors.forename: Claude
authors.initials: C
authors.lastname: Messier
authors.forename: David J
authors.initials: DJ
authors.lastname: Picketts
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000196:embryology* / Q000378:metabolism*; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D051858:Forkhead Transcription Factors / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D013234:Stem Cells / Q000166:cytology*; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C489565:Foxg1 protein, mouse; D009419:Nerve Tissue Proteins; C499335:Smarca1 protein, mouse; D014157:Transcription Factors