The Notch and Wnt signalling pathways are used during animal development to generate a diverse array of cell types. The two pathways often have opposing effects on cell-fate decisions but some cells receive inputs from both pathways simultaneously. In these circumstances, it is common for the receiving cell to exhibit a Wnt-ON/Notch-OFF response but how is this response generated? Now, on p. , Keith Brennan and co-workers report that Wnt acts via Dishevelled, a key mediator of Wnt/β-catenin signalling, to inhibit the Notch pathway and that this crosstalk controls cell-fate specification during Xenopus epidermal development in vivo. Dishevelled, they report, binds and directly inhibits the CSL (CBF1, Suppressor of Hairless, Lag-1; RBPJκ in mice) transcription factors that mediate Notch signalling. Moreover, this crosstalk mechanism is conserved between vertebrates and invertebrates. Thus, by acting as both an activator of Wnt signalling and an inhibitor of Notch signalling, Dishevelled sharpens the distinction between opposing Wnt and Notch responses, thereby ensuring that robust cell-fate decisions are taken during development.
