The neural crest is an embryonic stem cell population whose migratory behaviour has been likened to malignant invasion. The neural crest, as does cancer, undergoes an epithelial-to-mesenchymal transition and migrates to colonize almost all the tissues of the embryo. Neural crest cells exhibit collective cell migration, moving in streams of high directionality. The migratory neural crest streams are kept in shape by the presence of negative signals in their vicinity. The directionality of the migrating neural crest is achieved by contact-dependent cell polarization, in a phenomenon called contact inhibition of locomotion. Two cells experiencing contact inhibition of locomotion move away from each other after collision. However, if the cell density is high only cells exposed to a free edge can migrate away from the cluster leading to the directional migration of the whole group. Recent work performed in chicks, zebrafish and frogs has shown that the non-canonical Wnt–PCP (planar cell polarity) pathway plays a major role in neural crest migration. PCP signalling controls contact inhibition of locomotion between neural crest cells by localizing different PCP proteins at the site of cell contact during collision and locally regulating the activity of Rho GTPases. Upon collision RhoA (ras homologue family member A) is activated, whereas Rac1 is inhibited at the contact between two migrating neural crest cells, leading to the collapse of protrusions and the migration of cells away from one another. The present review summarizes the mechanisms that control neural crest migration and focuses on the role of non-canonical Wnt or PCP signalling in this process.
- cell migration
- contact inhibition of locomotion
- neural crest cell
- planar cell polarity
- Wnt signalling
Abbreviations: DS, Dachsous; Dsh, Dishevelled; EMT, epithelial–mesenchymal transition; FGF, fibroblast growth factor; FJ, Four-jointed; Fmi, Flamingo; FT, Fat; Fz, Frizzled; GSK3β, glycogen synthase kinase 3β; Nrp, neuropilin; PCP, planar cell polarity; PTK7, protein tyrosine kinase 7; ROCK, Rho-associated kinase
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