Notch signalling is essential for many aspects of development, including the mechanism of lateral inhibition, where cells that adopt a particular fate prevent adjacent cells from doing likewise. The endocytosis of the Notch ligand Delta is important for lateral inhibition and is regulated in zebrafish by the ubiquitin ligase Mind bomb 1 (Mib1). Now, Matsuda and Chitnis reveal that the endocytosis of certain zebrafish Delta homologues, such as DeltaD,crucially depends on their interaction with Notch itself and leads to their subsequent degradation (see ). The authors report that DeltaD, which normally predominantly localises to the cytoplasm, instead localises to the plasma membrane in mib1 mutants and notch morphants. This is because DeltaD endocytosis depends on Notch-DeltaD interactions, regardless of whether Notch is expressed in the same (in cis) or in adjacent cells (in trans). Interactions in cis, however, are probably inhibitory, whereas interactions in trans activate Notch signalling in the adjacent cells, suggesting a mechanism whereby this process might contribute to lateral inhibition.
