Control of neural crest cell fate by the Wnt signalling pathway

Environmental signals are important in the development of neural crest, during which process multipotent progenitor must choose from several fates(1-3). However, the nature of these environmental signals is unknown. A previous fate map of zebrafish cranial neural crest showed that lineage-restricted clones of pigment cells arise hom medial cells near the neural keel, and that clones of neurons arise from lateral cells farther from the neural keel(4), Wnt-1 and Wnt-3a are candidate genes for influencing neural crest fate, as they are expressed next to medial, but not lateral, crest cells. Here we determine the role of Wnt signals in modulating the fate of neural crest by injecting messenger RNAs into single, premigratory neural crest cells of zebrafish, Lineage analysis of injected cells shows that activation of Wnt signalling by injection of mRNA encoding cytoplasmic beta-catenin promotes pigment-cell formation at the expense of neurons and glia. Conversely, inhibition of the Wnt pathway, by injection of mRNAs encoding either a truncated form of the transcription factor Tcf-3 or a dominant-negative Wnt, promotes neuronal fates at the expense of pigment cells. We conclude that endogenous Wnt signalling normality promotes pigment-cell formation by medial crest cells and thereby contributes to the diversity of neural crest cell fates.