Brahma-related gene 1 has time-specific roles during brain and eye development

ABSTRACT During development, gene expression is tightly controlled to facilitate the generation of diverse cell types that form central nervous system. Brahma-related 1 (Brg1, also known as Smarca4) catalytic subunit SWItch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex regulates transcription. We investigated role Brg1 between embryonic day 6.5 (E6.5) and E14.5 in Sox2-positive neural stem cells (NSCs). Being without major consequences at E6.5 E14.5, loss E7.5 E12.5 resulted formation rosette-like structures subventricular zone, well morphological alterations enlargement retina (NR). Additionally, Brg1-deficient showed decreased survival vitro vivo. Furthermore, we uncovered distinct changes upon loss, pointing towards impaired neuron functions, especially those involving synaptic communication altered composition extracellular matrix. Comparison with mice deficient for integrase interactor (Ini1, Smarcb1) revealed enlarged NR was specific not caused by a general dysfunction SWI/SNF complex. These results suggest crucial NSCs during brain eye development.