Two distinct Wnt signalling pathways regulate many important developmental processes during embryogenesis. The canonical pathway acts throughβ-catenin to control cell fate determination, whereas the non-canonical pathway modulates morphogenetic movements by regulating the actin cytoskeleton. But how do developing tissues switch between these pathways? On , Kibardin and colleagues propose that metastasis-associated kinase (MAK) may do the switching during Xenopus development. In loss-of-function and gain-of-function experiments, the researchers show that MAK is required for convergent extension movements, eye development and specification of the midbrain/hindbrain boundary, all of which are controlled by Wnt signalling. MAK, they report, stimulates non-canonical Wnt signalling but negatively regulates the canonical pathway. These effects require its kinase activity,one possible substrate of which is Dishevelled, which functions in both Wnt signalling branches. The researchers propose, therefore, that MAK may switch Wnt signalling from the canonical to the non-canonical pathway during development through phosphorylation of Dishevelled. Future research should uncover what regulates MAK activity.
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