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

Kathleen Wung Bi-Lin,Pratap Veerabrahma Seshachalam,Anastassia Stoykova,Sujoy Ghosh,Tran Tuoc,Manvendra K. Singh,Frank L. Conlon

doi:10.1371/journal.pgen.1009446

Abstract

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.

Highlights

Neural crest cells (NCCs) are a group of multipotent cells that are transiently generated along the vertebrate axis
To determine the role of the Brm-associated factors (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

Summary

Introduction

Neural crest cells (NCCs) are a group of multipotent cells that are transiently generated along the vertebrate axis. NCCs migrate from the dorsolateral edges of the neural plate before the formation of the neural tube These NCCs undergo an epithelial-tomesenchymal transition to delaminate and migrate through the extracellular space to multiple tissues and differentiate into various cell types including neurons, pigment cells, cartilage, bone, and smooth muscle of the cardiovascular system in the developing embryo. Depending upon their location along the anterior-posterior body axis and differentiation ability to form certain derivatives, NCCs can be subdivided into five axial populations: cranial, cardiac, vagal, trunk, and sacral NCCs. Cranial NCCs migrate and populate the face and the first and second pharyngeal arches, contributing to the cranial ganglia, craniofacial skeleton, palates, and other structures of the developing head. Genetic or environmental factors affecting NCCs ability to proliferate, migrate, or differentiate leads to many congenital cardiovascular and craniofacial disorders and contribute to more than one-third of all congenital diseases in humans

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