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Dev Cell. 2017 Jan 23;40(2):168-184. doi: 10.1016/j.devcel.2016.12.004. Epub 2016 Dec 29.

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

Author information

1
CytoMorpho Lab, A2T, UMRS1160, Institut Universitaire d'Hématologie, Hôpital Saint Louis, INSERM/AP-HP/Université Paris Diderot, 1 Avenue Claude Vellefaux, 75010 Paris, France; CytoMorpho Lab, LPCV, UMR5168, Biosciences & Biotechnology Institute of Grenoble, CEA/INRA/CNRS/Université Grenoble-Alpes, 17 rue des Martyrs, 38054 Grenoble, France; CYTOO SA, 7 Parvis Louis Néel, 38040 Grenoble, France.
2
CytoMorpho Lab, LPCV, UMR5168, Biosciences & Biotechnology Institute of Grenoble, CEA/INRA/CNRS/Université Grenoble-Alpes, 17 rue des Martyrs, 38054 Grenoble, France.
3
MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK.
4
GABI, INRA/AgroParisTech/Université Paris-Saclay, Domaine de Vilvert, 78352 Jouy-en-Josas, France.
5
CytoMorpho Lab, A2T, UMRS1160, Institut Universitaire d'Hématologie, Hôpital Saint Louis, INSERM/AP-HP/Université Paris Diderot, 1 Avenue Claude Vellefaux, 75010 Paris, France.
6
CYTOO SA, 7 Parvis Louis Néel, 38040 Grenoble, France.
7
Laboratoire de Biologie du Cancer et de l'Infection, UMRS1036, Biosciences & Biotechnology Institute of Grenoble, CEA/INSERM/Université Grenoble-Alpes, 17 rue des Martyrs, 38054 Grenoble, France.
8
CytoMorpho Lab, A2T, UMRS1160, Institut Universitaire d'Hématologie, Hôpital Saint Louis, INSERM/AP-HP/Université Paris Diderot, 1 Avenue Claude Vellefaux, 75010 Paris, France; CytoMorpho Lab, LPCV, UMR5168, Biosciences & Biotechnology Institute of Grenoble, CEA/INRA/CNRS/Université Grenoble-Alpes, 17 rue des Martyrs, 38054 Grenoble, France. Electronic address: manuel.thery@cea.fr.

Abstract

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.

KEYWORDS:

EMT; centrosome; cytoskeleton; intercellular junctions; micropatterning; microtubule; migration; polarity; stathmin

PMID:
28041907
PMCID:
PMC5497078
DOI:
10.1016/j.devcel.2016.12.004
[Indexed for MEDLINE]
Free PMC Article

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