Snf2l Regulates Foxg1-Dependent Progenitor Cell Expansion in the Developing Brain

摘要

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. Yip et al. identify the chromatin remodeler Snf2l as an upstream regulator of . Foxg1, a key determinant of telencephalon development. Inactivation of Snf2l derepresses . Foxg1 expression, thereby accelerating progenitor proliferation, delaying neurogenesis, and increasing total neuronal output.