In vertebrates, the peripheral nervous system is embryologically derived from the neural crest. Although the earliest neural crest cells seem to be multipotent, the molecular mechanisms responsible for the restriction of these cells to different sublineages are not understood. We therefore searched for developmental control genes expressed in crest cells or their derivatives. One important class of regulatory molecules comprises proteins with common DNA-binding and dimerization domains, the basic helix-loop-helix (B-HLH) region. Members of this family include MyoD, a mammalian myogenic determination molecule, and proteins encoded by genes of the achaete-scute complex of Drosophila, which have an important role in neuronal determination. From a sympathetic neuronal precursor cell line derived from the neural crest we have now isolated two different mammalian genes that are homologous to genes of the achaete-scute complex. The sequence of the B-HLH-encoding region of these genes is more similar to that of the genes of the achaete-scute complex than it is to that of other, mammalian members of the B-HLH family. At least one of these genes is transiently expressed in the embryonic rat nervous system, is not detected in non-neuronal tissues or cell lines, and is induced by nerve growth factor in PC12 cells.