Two transcription factors with a helix-loop-helix motif, human achaete-scute homologue-1 (hASH1) and hairy/enhancer of split homologue-1 (HES1), are essential for proper neuronal development. hASH1 is constitutively expressed in the most virulent human lung cancer, small cell lung cancer (SCLC), which exhibits neuroendocrine (NE) features. Moreover, hASH1 is essential for development of normal pulmonary NE cells that resemble SCLC. HES1 acts to transcriptionally repress hASH1 expression. The repressive effect of HES1 is mediated by binding of the protein to a class C site in the hASH1 promoter. HES1 also plays a role in mid- and hindbrain development, and in Notch signaling in thymocytes.