Critical role of the BAF chromatin remodeling complex during murine neural crest development

Author summary Neural crest cells (NCCs) are a multipotent and migratory cell population that is induced at the neural plate border during neurulation and contributes to the formation of a wide range of tissues. Defects in the development, differentiation, or migration of NCCs lead to various birth defects including craniofacial and heart anomalies. Here, by genetically deleting BAF155/BAF170, the core subunits required for the assembly, stability, and functions of the BAF chromatin remodeling complex, we demonstrate that the BAF complex is essential for the proliferation, survival, and differentiation of the NCCs. Neural crest-specific deletion of BAF155/BAF170 leads to embryonic lethality due to a wide range of developmental defects including craniofacial and cardiovascular defects. By performing RNAseq and transcription factor enrichment analysis we show that the BAF complex modulates the expression of multiple signaling pathway genes including Hippo and Notch, essential for the development of the NCCs. Furthermore, the BAF complex component physically interacts with the Hippo signaling components in NCCs to regulate gene expression. We demonstrated that the BAF complex is essential for the Brg1-Yap-Tead-dependent transcription of target genes in NCCs. Together, our results demonstrate a critical role of the BAF complex in modulating the gene regulatory network essential for the proper development of neural crest and neural crest-derived tissues. 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 of the BAF complex, we deleted BAF155/BAF170, the core subunits required for the assembly, stability, and functions of the BAF complex in neural crest cells (NCCs). Neural crest-specific deletion of BAF155/BAF170 leads to embryonic lethality due to a wide range of developmental defects including craniofacial, pharyngeal arch artery, and OFT defects. RNAseq and transcription factor enrichment analysis revealed that the BAF complex modulates the expression of multiple signaling pathway genes including Hippo and Notch, essential for the migration, proliferation, and differentiation of the NCCs. Furthermore, we demonstrated that the BAF complex is essential for the Brg1-Yap-Tead-dependent transcription of target genes in NCCs. Together, our results demonstrate an important role of the BAF complex in modulating the gene regulatory network essential for neural crest development.

Automated summary

The BAF complex is crucial for the proliferation, survival, and differentiation of neural crest cells (NCCs), with specific deletion of BAF155/BAF170 leading to embryonic lethality and various developmental defects. The complex modulates the expression of multiple signaling pathway genes essential for NCC development, demonstrating an important role in the gene regulatory network.