The SWI/SNF Complex in Neural Crest Cell Development and Disease

While the neural crest cell population gives rise to an extraordinary array of derivatives, including elements of the craniofacial skeleton, skin pigmentation, and peripheral nervous system, it is today increasingly recognized that Schwann cell precursors are also multipotent. Two mammalian paralogs of the SWI/SNF (switch/sucrose nonfermentable) chromatin-remodeling complexes, BAF (Brg1-associated factors) and PBAF (polybromo-associated BAF), are critical for neural crest specification during normal mammalian development. There is increasing evidence that pathogenic variants in components of the BAF and PBAF complexes play central roles in the pathogenesis of neural crest-derived tumors. Transgenic mouse models demonstrate a temporal window early in development where pathogenic variants in Smarcb1 result in the formation of aggressive, poorly differentiated tumors, such as rhabdoid tumors. By contrast, later in development, homozygous inactivation of Smarcb1 requires additional pathogenic variants in tumor suppressor genes to drive the development of differentiated adult neoplasms derived from the neural crest, which have a comparatively good prognosis in humans.

Automated summary

The neural crest cell population has the potential to differentiate into various structures, such as craniofacial skeleton, skin pigmentation, and peripheral nervous system. The BAF and PBAF complexes, paralogs of the SWI/SNF chromatin-remodeling complexes, play critical roles in neural crest specification during mammalian development. Pathogenic variants in components of these complexes have been found to be involved in the pathogenesis of neural crest-derived tumors. In mouse models, early pathogenic variants in Smarcb1 lead to aggressive and poorly differentiated tumors, while later in development, additional pathogenic variants in tumor suppressor genes are required for the development of differentiated adult neoplasms derived from the neural crest.