Hey bHLH Factors in Cardiovascular Development

Notch signal transduction is involved in a broad varietyof developmental decisions throughout the animal kingdom. Nevertheless, there are only a small number ofdownstream effectors, most notably the Hes family of basic helix-loop-helix (bHLH) proteins that are known tomediate such signals (Davis and Turner 2001). The Heygene family, which encodes a new subclass of hairy/Enhancer-of-split-related bHLH transcriptional regulators,represents a novel set of mediators for Notch signalingevents. Hey genes are dynamically expressed duringmouse development with an emphasis on somitogenesis,neurogenesis, and cardiac and vascular morphogenesis.Hey proteins can dimerize with multiple partners, andthey show specific binding to a subset of E-box sequences. The most prominent features of Hey proteins,bHLH and orange domains and a characteristic carboxylterminus, are depicted schematically in Figure 1. Severallines of evidence suggest that they are intimately involved in several aspects of cardiovascular development...