The Notch signalling system: recent insights into the complexity of a conserved pathway

The Notch signalling network is highly conserved in Metazoa and is crucial for various cell-fate decisions. Focusing onDrosophila melanogaster, this Review summarizes and integrates various recent studies, including large-scale genetic and proteomic screens that have provided a new appreciation of the complexity of Notch signalling. Notch signalling links the fate of one cell to that of an immediate neighbour and consequently controls differentiation, proliferation and apoptotic events in multiple metazoan tissues. Perturbations in this pathway activity have been linked to several human genetic disorders and cancers. Recent genome-scale studies in Drosophila melanogaster have revealed an extraordinarily complex network of genes that can affect Notch activity. This highly interconnected network contrasts our traditional view of the Notch pathway as a simple linear sequence of events. Although we now have an unprecedented insight into the way in which such a fundamental signalling mechanism is controlled by the genome, we are faced with serious challenges in analysing the underlying molecular mechanisms of Notch signal control.