Protein zero gene expression is regulated by the glial transcription factor Sox10

Myelinating glia express high levels of a unique set of genes which code fo r structural proteins of the myelin sheath, Few transcription factors have so far been implicated in the regulation of ally myelin gene. Here we show that the protein zero (P-o) gene, a myelin gene exclusively expressed in th e Schwann cell lineage of the peripheral nervous system, is controlled in i ts expression by the high-mobility-group domain protein Sox10 both in tissu e culture and in vivo. Induction of wild-type Sox10, but not of other trans cription factors or Sox10 mutants, strongly increased endogenous P-o expres sion in tissue culture. This activation was mediated by the P-o promoter, w hich was stimulated by Sox10 in transient transfections. Detailed analyses revealed the involvement of a proximal and a distal promoter region. The di stal region functioned only in conjunction with the proximal one and contai ned a single Sos consensus binding site, which accounted for most of its ac tivity. In contrast, the proximal region mediated Sox10 responsiveness on i ts own. It contained multiple binding sites far Sos proteins, with two high -affinity sites being the most significant. P-o expression also depended on Sox10 in vivo, as evident from the analysis of Schwann cell precursors in mouse embryos with Sox10 mutation at day 12.5 of embryogenesis. To our know ledge this is the most conclusive link to date between a glial transcriptio n factor and cell-specific activation of myelin gene expression.