Notch receptor signaling: From flies to mammals

During embryonic development, cellular fate is determined by various types of extracellular signals. A mechanism known as lateral inhibition controls the ability of cells to respond to these various differentiation signals. One of the best studied example is the Notch activation pathway, which controls the differentiation of numerous cell types during development of Drosophila and C. elegans. During embryonic neurogenesis in Drosophila, Notch receptor activation results in transcriptional activation of target genes and inhibition of differentiation. Genetic approaches in flies and worms have defined putative components of this signaling cascade, including factors that may associate with the Notch intracellular domain required for signaling activity. One of them, the Su(H) protein, is a transcription factor which binds to the regulatory sequences of several Notch target genes. It has been suggested that the intracellular domain of Notch might sequester Su(H) in the cytoplasm, and that Notch receptor activation might lead to the release of Su(H) and to its nuclear import. Recent data obtained in vertebrates suggest that the Notch pathway is conserved, both structurally and functionally. On the basis of these results, a model has been proposed, whereby the intracellular domain of Notch, following a proteolytic event, would translocate to the nucleus and directly activate transcription of its target genes by binding to the Su(H) protein.