SCG10 is a growth-associated protein that is expressed early in the development of neuronal derivatives of the neural crest. We describe here the isolation of the SCG10 chromosomal gene and the identification of regulatory regions that control its expression. The SCG10 transcription unit spans approximately 40 kb. Like other neural-specific genes, SCG10 contains multiple transcription initiation sites. The gene contains a constitutive enhancer-like element in the promoter-proximal region and a silencer located farther upstream. This silencer preferentially suppresses the activity of the enhancer in nonneuronal cells. Furthermore, the silencer is able to confer such preferential suppression upon a heterologous promoter in an orientation-independent manner. These data suggest that the expression of SCG10 in neuronal cells depends predominantly upon specific derepression.