MMP14 is required for delamination of chick neural crest cells independently of its catalytic activity.

Matrix metalloproteinases have a broad spectrum of substrates ranging from extracellular matrix components and adhesion molecules to chemokines and growth factors. Despite being mostly secreted, MMPs have been detected in the cytosol, the mitochondria or the nucleus. Although most of the attention is focused on their role in matrix remodeling, the diversity of their substrates and their complex trafficking open the possibility for non-canonical functions. Yet in vivo examples and experimental demonstration of the physiological relevance of such activities are rare. Here, we have used chick neural crest (NC) cells, a highly migratory stem cell population likened to invasive cancer cells, as a model for physiological epithelial-mesenchymal transition (EMT). We demonstrate that MMP14 is required for NC delamination. Interestingly, this role is independent of its cytoplasmic tail and of its catalytic activity. Our in vivo data indicate that, in addition to being a late pro-invasive factor, MMP14 is also likely to be an early player, owing to its role in EMT.

Neural crest delamination and migration: Looking forward to the next 150 years.

Neural crest (NC) cells were described for the first time in 1868 by Wilhelm His. Since then, this amazing population of migratory stem cells has been intensively studied. It took a century to fully unravel their incredible abilities to contribute to nearly every organ of the body. Yet, our understanding of the cell and molecular mechanisms controlling their migration is far from complete. In this review, we summarize the current knowledge on epithelial-mesenchymal transition and collective behavior of NC cells and propose further stops at which the NC train might be calling in the near future.