Notch signalling in context

The Notch signalling pathway functions in many processes — from developmental patterning to cell growth and cell death. As the complexity of Notch signalling regulation is being unravelled at the levels of cell-surface ligand–receptor interactions and of gene expression, we are gaining a deeper understanding of how this conserved pathway can lead to such diverse cellular responses. The highly conserved Notch signalling pathway functions in many different developmental and homeostatic processes, which raises the question of how this pathway can achieve such diverse outcomes. With a direct route from the membrane to the nucleus, the Notch pathway has fewer opportunities for regulation than do many other signalling pathways, yet it generates exquisitely patterned structures, including sensory hair cells and branched arterial networks. More confusingly, its activity promotes tissue growth and cancers in some circumstances but cell death and tumour suppression in others. Many different regulatory mechanisms help to shape the activity of the Notch pathway, generating functional outputs that are appropriate for each context. These mechanisms include the receptor–ligand landscape, the tissue topology, the nuclear environment and the connectivity of the regulatory networks.