Human neural crest (NC) cells are the precursors for a wide range of ectodermal and mesenchymal cell derivatives. Due to the inherent difficulties associated with early human embryonic studies, it is currently unclear exactly when NC cells are specified and from what. Differentiation of human embryonic stem cells represents an excellent in vitro system to study NC induction; however, current protocols often involve cell conglomerates and/or undefined media, making it difficult to tease apart the key signalling events that drive induction. Now, on p. , Martín García-Castro and colleagues report a highly efficient, defined protocol for human NC induction and use this system to identify a population of cells, which they call ʻpre-neural plate borderʼ cells, that represent the earliest known stage of NC specification. WNT-induced molecular markers are used to characterise this population, which the authors show is specified distinct from ectoderm and mesodermal fates. The authors further demonstrate a crucial role for WNT/β-catenin signalling, as well as the dynamic effects of BMP and FGF signalling, in NC induction. These results support the in vivo origin of NC cells from non-neural progenitors and provide strong evidence for the key role played by WNT/β-catenin in human NC induction.
