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Background  The  ERBB3  gene is essential for the proper development of the neural crest (NC) and its derivative populations such as Schwann cells. As with all cell fate decisions, transcriptional regulatory control plays a significant role in the progressive restriction and specification of NC derived lineages during development. However, little is known about the sequences mediating transcriptional regulation of  ERBB3  or the factors that bind them.    Results  In this study we identified three transcriptional enhancers at the  ERBB3  locus and evaluated their regulatory potential  in vitro  in NC-derived cell types and  in vivo  in transgenic zebrafish. One enhancer, termed  ERBB3 _MCS6, which lies within the first intron of  ERBB3 , directs the highest reporter expression  in vitro  and also demonstrates epigenetic marks consistent with enhancer activity. We identify a consensus SOX10 binding site within  ERBB3 _MCS6 and demonstrate,  in vitro , its necessity and sufficiency for the activity of this enhancer. Additionally, we demonstrate that transcription from the endogenous  Erbb3  locus is dependent on Sox10. Further we demonstrate  in vitro  that Sox10 physically interacts with that  ERBB3 _MCS6. Consistent with its  in vitro  activity, we also show that  ERBB3 _MCS6 drives reporter expression in NC cells and a subset of its derivative lineages  in vivo  in zebrafish in a manner consistent with  erbb3b  expression. We also demonstrate, using morpholino analysis, that Sox10 is necessary for  ERBB3 _MCS6 expression  in vivo  in zebrafish.    Conclusions  Taken collectively, our data suggest that  ERBB3  may be directly regulated by SOX10, and that this control may in part be facilitated by  ERBB3 _MCS6.

SOX10 directly modulates ERBB3 transcription via an intronic neural crest enhancer