Notch, a transmembrane receptor, is best known for mediating lateral inhibition — a mechanism that allows neighbouring cells to adopt one of two different cell fates. Consistent with the function of Notch in preventing neural fate, lateral inhibition through Notch specifies the number and positioning of microchaetae—short sensory bristles — on the adult body of the fly. When Ramain and colleagues characterized several dominant Notch mutants (NMcd) that they had identified in a genetic screen for loss of microchaetae, they were surprised to find that the mutant phenotype was independent of the classical lateral inhibition pathway. So how is the Notch signal transduced in microchaetae? Previous reports indicated that the cytoplasmic protein Deltex (Dx) can bind to the intracellular portion of Notch; Ramain et al. showed that mutations in Dx suppress the NMcd gain-of-function phenotypes, indicating that this non-canonical Notch pathway requires Dx.
This new microchaetae-repressing function of Notch would be expected to be inhibited in wild-type flies. Dishevelled (Dsh), another component of the Wingless pathway, had been previously reported to interact physically with Notch, and so the authors proposed that Dsh antagonizes the Dx-dependent function of Notch on the adult body. In vivo and in vitro analysis showed not only that Dsh is involved, but also that it binds to the intracellular portion of Notch that is missing in the NMcd mutant proteins.
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