Dev. Cell 2012 Apr
Yip DJ, Corcoran CP, Alvarez-Saavedra M, DeMaria A, Rennick S, Mears AJ, Rudnicki MA, Messier C, Picketts DJ
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, increa
...[more]sed 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.
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Mesh Headings:
Amino Acid Sequence, Animals, Brain, Cell Cycle, Cell Differentiation, Cell Proliferation, Cells, Cultured, Chromatin Immunoprecipitation, DNA-Binding Proteins, Embryo, Mammalian, Female, Fluorescent Antibody Technique, Forkhead Transcription Factors, Gene Expression Regulation, Developmental, Male, Mice, Mice, Knockout, Molecular Sequence Data, Nerve Tissue Proteins, Neurogenesis, Sequence Homology, Amino Acid, Stem Cells, Transcription Factors