Spatial regulation of signalling pathways during development is essential. In the Drosophila leg, a stripe of cells in each segment expresses the Notch ligand Serrate (Ser) and activates the Notch pathway, which is required to specify joints, in distal cells only. Now, on p. , Sarah Bray, Máximo Ibo Galindo and co-workers reveal that the planar cell polarity (PCP) proteins Frizzled and Dishevelled control this spatial restriction of Notch activation. The researchers show that these PCP proteins are enriched at the distal side of cells in the developing leg and that elimination of PCP gene function in the cells proximal to the Ser-expressing cells alleviates Notch signalling repression, resulting in ectopic joint formation. Mutants that disrupt a direct interaction between Dishevelled and Notch also reduce the efficacy of repression, whereas increased levels of Rab5, an endocytic regulator, suppress ectopic joint formation. Thus, the researchers conclude, PCP controls directional Notch signalling in the Drosophila leg by regulating the endocytic trafficking of Notch.
