Journal
DEVELOPMENTAL CELL
Volume 40, Issue 2, Pages 168-184Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2016.12.004
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Funding
- ERC (SpiCy) [StG-310472]
- BPI France (ETICS) [I1107018W]
- ANRT [CIFRE 2011/1730]
- Laboratory of Excellence (Grenoble Alliance for Integrated Structural Cell Biology)
- Wellcome Trust
- La Ligue Nationale et Regionale contre le Cancer
- Espoir Foundation
- Medical Research Council [MR/K017047/1] Funding Source: researchfish
- MRC [MR/K017047/1] Funding Source: UKRI
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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 micro tubule 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.
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