Arbiter of differentiation and death: Notch signaling meets apoptosis

Notch-ligand interactions are a highly conserved mechanism that regulates c ell fate decisions. Over the past few years, numerous observations have sho wn that this mechanism operates to regulate cell differentiation in an enor mous variety of developmental and cell maturation processes. Recent studies indicate that in addition to cell differentiation, Notch signaling has dir ect effects on proliferation and programmed cell death. The picture emergin g from these findings suggests that, depending on cellular and developmenta l context, Notch signaling may function as a general "arbiter" of cell fate , regulating differentiation potential, rate of proliferation, and apoptoti c cell death. In this review, we briefly summarize the current knowledge of the structure and function of Notch receptors and discuss the recent evide nce that Notch signaling regulates apoptotic cell death. The possible mecha nisms of this effect and its potential implications for developmental biolo gy, immunobiology, neuropathology, and tumor biology are discussed. (C) 199 9 Wiley-Liss, Inc.