The BAF chromatin remodeling complex regulates gene expression programs essential for mammalian neural crest development
Neural crest cells (NCCs) are a multipotent cell population that contributes to the development  of many tissues including craniofacial, pharyngeal arch arteries, and cardiac outflow tract  (OFT). The BAF complex plays an important role in the development of a wide range of tissues  by modulating gene expression programs at the chromatin level. However, its role in neural  crest development has remained unclear. To determine the role BAF complex, we deleted  BAF155 and BAF170, the core subunits required for the assembly, stability, and functions of  the BAF complex in NCCs. Mouse embryos lacking BAF155/170 in NCCs displayed early  lethality due to a wide range of developmental defects including craniofacial defects,  pharyngeal arch artery defects, and OFT defects. We observed reduced proliferation,  increased cell death, and impaired migration of cardiac NCCs to the OFT in BAF155/170  mutants. RNAseq analysis on sorted NCCs revealed that the BAF complex regulates the  expression of numerous genes essential for neural crest development. We observed  downregulation of Hippo and Notch signaling pathways, both essential for the migration,  proliferation, and differentiation of the NCCs. The BAF complex interacts with transcription  factors to modulate the transcriptional program. Therefore, we performed transcription factor  enrichment analysis on the RNAseq data set and identified several transcription factors  including Hey1, Hey2, and Hes5 that may directly or indirectly interact with the BAF complex  in NCCs. We also found that Brg1 interact with Tead transcription factors and the interaction  was impaired in BAF155/170 knockdown cells. Together, our results demonstrate an  important role of the BAF complex in modulating the gene regulatory network essential for  neural crest development. Overall design: 6 samples are analyzed comprises of control (n = 3) and mutant (n = 3)