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Dissection of Xenopus laevis Neural Crest for in vitro Explant Culture or in vivo Transplantation
Published on: March 4, 2014
MMP14 is required for delamination of chick neural crest cells independently of its catalytic activity
Cyril Andrieu1, Audrey Montigny1, Anne Bibonne1
1Centre de Biologie du Développement, Centre de Biologie Intégrative, Université de Toulouse, CNRS, UPS, Toulouse, 31062, France.
Abstract:
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.
Insights
Matrix metalloproteinases (MMPs), specifically MMP14, play a crucial role in epithelial-mesenchymal transition (EMT) and neural crest cell delamination. This study reveals MMP14
Area of Science:
- Cell Biology
- Developmental Biology
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) are enzymes primarily known for extracellular matrix remodeling.
- MMPs exhibit diverse substrates and complex trafficking, suggesting non-canonical functions beyond matrix degradation.
- Examples of MMPs' non-canonical functions and their physiological relevance in vivo are scarce.
Purpose of the Study:
- To investigate the role of MMP14 in physiological epithelial-mesenchymal transition (EMT) using chick neural crest (NC) cells as a model.
- To determine if MMP14's function in NC delamination is dependent on its catalytic activity or cytoplasmic tail.
Main Methods:
- Utilized chick neural crest (NC) cells as a model system for epithelial-mesenchymal transition (EMT).
- Conducted in vivo experiments to assess the requirement of MMP14 in NC delamination.
- Investigated the functional domains of MMP14 (cytoplasmic tail, catalytic activity) in relation to its role in NC delamination.
Main Results:
- MMP14 is essential for neural crest (NC) cell delamination during epithelial-mesenchymal transition (EMT).
- This critical role of MMP14 in NC delamination is independent of its catalytic activity and cytoplasmic tail.
- MMP14 functions as an early regulator in EMT, not solely a late-stage pro-invasive factor.
Conclusions:
- MMP14 plays a significant, non-canonical role in early developmental processes like EMT and cell delamination.
- The findings expand the understanding of MMP14's functions beyond matrix remodeling, highlighting its importance in cell migration and development.
- MMP14 is identified as an early player in EMT, contributing to the migratory potential of neural crest cells.
