CONTROL OF NEURAL CREST CELL FATE BY THE WNT SIGNALING 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 unk nown. A previous fate map of zebrafish cranial neural crest showed tha t lineage-restricted clones of pigment cells arise hom medial cells ne ar the neural keel, and that clones of neurons arise from lateral cell s farther from the neural keel(4), Wnt-1 and Wnt-3a are candidate gene s for influencing neural crest fate, as they are expressed next to med ial, but not lateral, crest cells. Here we determine the role of Wnt s ignals in modulating the fate of neural crest by injecting messenger R NAs 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, inhibit ion of the Wnt pathway, by injection of mRNAs encoding either a trunca ted 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 formati on by medial crest cells and thereby contributes to the diversity of n eural crest cell fates.