Abstract
Schwann cells produce myelin sheaths and thereby permit rapid saltatory conductance in the vertebrate peripheral nervous system. Their stepwise differentiation from neural crest cells is driven bya defined setof transcription factors. How this is linked to chromatin changes is not well understood. Here we show that the glial transcription factor Sox10 functions in Schwann cells by recruiting Brg1-containingchromatin-remodeling complexes via Baf60a toregulatory regions of Oct6 and Krox20 genes. Itthereby stimulates expression of these transcriptional regulators that then cooperate with Sox10 toconvert immature into myelinating Schwann cells.The functional interaction between Sox10 andBrg1 is evident from gain- and loss-of-function studies, similar neuropathies in the corresponding mouse mutants, and an aggravated neuropathy in compound mutants. Our results demonstrate that the transcription factor-mediated recruitment of thechromatin-remodeling machinery to specific genomic loci is an essential driving force for Schwann cell differentiation and myelination.
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