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Polarity reversal by centrosome repositioning primes cell scattering

In collaboration with researchers from the Cell & Plant Physiology laboratory at our institute, we demonstrated that the repositioning of the centrosome in epithelial cells primes the migration of cells during the the epithelial-mesenchymal transition and then dissected the chronology of the cellular events of this reversal of polarity.

Published on 7 April 2017
The epithelium constitutes a barrier delimiting the secretory structures in which the cells are oriented and polarized. During the development of the embryo but also in pathological conditions (fibrosis, cancer), these epithelial cells migrate by converting themselves into so-called mesenchymal cells. This process called Epithelial-to-Mesenchymal Transition (EMT), not only involves reorganization of cell position and acquisition of a migratory phenotype but also implies a reorientation of cell function and polarity.

To investigate the spatial coordination of intracellular reorganization with morphological changes, we monitored centrosome positioning during EMT in vivo, in developing mouse embryos and mammary gland, and in vitro, in cultured 3D cell aggregates (acini) and micropatterned cell doublets. 

Whatever the system studied, the centrosome leaves its position close to the inter-cellular junctions to refocus itself in front of the new zones of adhesion that allow the movement of the cell. This process requires a controlled microtubule disassembly, resulting in an effective internal polarity reversal. These observations show that during EMT, specific factors, but also the rigidity of the substrate of the cells, induce a reversion of the cellular polarity. Finally, thanks to the use of dynamic micropatterns, the chronology of these cellular events has been dissected showing that centrosome repositioning precedes cell migration.

These results reveal that the geometry of the centrosome-microtubule network adapts in response to the environment. Given the importance of cellular plasticity during embryogenesis and in pathologic conditions, this work represents an important contribution in understanding the molecular mechanisms underlying the process of EMT.
Schematic representation of the polarity reversal of a static cell (epithelial cell with an apico-basal orientation), towards a cell (mesenchymatous) that moves according to the direction of migration. During the EMT, factors such as TGFß or HGF as well as the rigidity of the substrate of the cells induce a reversion of the cellular polarity. The position of the centrosome is regulated by the number of microtubules in the cell. The repositioning of the centrosome precedes the diffusion of the cells.
Centrosome = Red dot.

The centrosome (red dot in the figure) is the organizing center of the microtubules (blue bundles) and thus of the skeleton of the cell.

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