Regulation of mammalian neural development by helix-loop-helix transcription factors

Understanding of the molecular mechanisms of mammalian neural development has been greatly advanced by identification and characterization of the molecules homologous to the factors regulating Drosophila neurogenesis, which provides a powerful model system. Studies of Drosophila show that transcription factors with a helix-loop-helix (HLH) domain play an essential role in neurogenesis. Several lines of evidence demonstrate that mammalian homologues of the Drosophila HLH factors do also play an essential role in neural development. Mash-1, a mammalian HLH factor homologous to the products of Drosophila proneural genes achaete-scute complex, is a positive regulator of neurogenesis and required for differentiation of olfactory and autonomic neurons. In addition, HES-1, another mammalian HLH factor homologous to the products of Drosophila hairy and Enhancer of split, antagonizes the activity of Mash-1 and negatively regulates neurogenesis. Thus, positive and negative HLH factors interact with each other, and the balance between them is important for the developmental processes. Recent studies show that many other HLH factors exist expressed in the developing mammalian nervous system. In this article, the authors review mammalian HLH factors expressed in the nervous system and discuss the molecular aspect of mammalian neurogenesis.