Polarity Reversal by Centrosome Repositioning Primes Cell Scattering during Epithelial-to-Mesenchymal Transition

Publication date: Available online 29 December 2016
Source:Developmental Cell
Author(s): Mithila Burute, Magali Prioux, Guillaume Blin, Sandrine Truchet, Gaëlle Letort, Qingzong Tseng, Thomas Bessy, Sally Lowell, Joanne Young, Odile Filhol, Manuel Théry
During epithelial-to-mesenchymal transition (EMT), cells lining the tissue periphery break up their cohesion to migrate within the tissue. This dramatic reorganization involves a poorly characterized reorientation of the apicobasal polarity of static epithelial cells into the front-rear polarity of migrating mesenchymal cells. 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 and micropatterned cell doublets. In all conditions, centrosomes moved from their off-centered position next to intercellular junctions toward extracellular matrix adhesions on the opposite side of the nucleus, resulting in an effective internal polarity reversal. This move appeared to be supported by controlled microtubule network disassembly. Sequential release of cell confinement using dynamic micropatterns, and modulation of microtubule dynamics, confirmed that centrosome repositioning was responsible for further cell disengagement and scattering.

Graphical abstract

Teaser

During epithelial-to-mesenchymal transition, epithelial cells migrate into the underlying interstitial tissues. Burute et al. show that this movement is enabled by a reversal of cell polarity. This reversal results from centrosome displacement from intercellular junctions to the cell center in response to controlled microtubule disassembly.


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