Delamination of neural crest cells requires transient and reversible Wnt inhibition mediated by DACT1/2.

Delamination of neural crest (NC) cells is a bona fide physiological model of epithelial-to-mesenchymal transition (EMT), a process that is influenced by Wnt/beta-catenin signalling. Using two in vivo models, we show that Wnt/beta-catenin signalling is transiently inhibited at the time of NC delamination. In attempting to define the mechanism underlying this inhibition, we found that the scaffold proteins Dact1 and Dact2, which are expressed in pre-migratory NC cells, are required for NC delamination in Xenopus and chick embryos, whereas they do not affect the motile properties of migratory NC cells. Dact1/2 inhibit Wnt/beta-catenin signalling upstream of the transcriptional activity of T cell factor (TCF), which is required for EMT to proceed. Dact1/2 regulate the subcellular distribution of beta-catenin, preventing beta-catenin from acting as a transcriptional coactivator to TCF, yet without affecting its stability. Together, these data identify a novel yet important regulatory element that inhibits beta-catenin signalling, which then affects NC delamination.