title: Polarity Reversal by Centrosome Repositioning Primes Cell Scattering during Epithelial-to-Mesenchymal Transition.
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.
authors.affiliation: 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.
authors.forename: Mithila
authors.initials: M
authors.lastname: Burute
authors.affiliation: CytoMorpho Lab, LPCV, UMR5168, Biosciences & Biotechnology Institute of Grenoble, CEA/INRA/CNRS/Université Grenoble-Alpes, 17 rue des Martyrs, 38054 Grenoble, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Prioux
authors.affiliation: 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.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Blin
authors.affiliation: GABI, INRA/AgroParisTech/Université Paris-Saclay, Domaine de Vilvert, 78352 Jouy-en-Josas, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Truchet
authors.affiliation: CytoMorpho Lab, LPCV, UMR5168, Biosciences & Biotechnology Institute of Grenoble, CEA/INRA/CNRS/Université Grenoble-Alpes, 17 rue des Martyrs, 38054 Grenoble, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Letort
authors.affiliation: CytoMorpho Lab, LPCV, UMR5168, Biosciences & Biotechnology Institute of Grenoble, CEA/INRA/CNRS/Université Grenoble-Alpes, 17 rue des Martyrs, 38054 Grenoble, France.
authors.forename: Qingzong
authors.initials: Q
authors.lastname: Tseng
authors.affiliation: CytoMorpho Lab, A2T, UMRS1160, Institut Universitaire d'Hématologie, Hôpital Saint Louis, INSERM/AP-HP/Université Paris Diderot, 1 Avenue Claude Vellefaux, 75010 Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bessy
authors.affiliation: 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.
authors.forename: Sally
authors.initials: S
authors.lastname: Lowell
authors.affiliation: CYTOO SA, 7 Parvis Louis Néel, 38040 Grenoble, France.
authors.forename: Joanne
authors.initials: J
authors.lastname: Young
authors.affiliation: 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.
authors.forename: Odile
authors.initials: O
authors.lastname: Filhol
authors.affiliation: 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.
authors.forename: Manuel
authors.initials: M
authors.lastname: Théry
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001696:Biomechanical Phenomena; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018797:Cell Cycle Proteins; D016764:Cell Polarity; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism*; D047108:Embryonic Development; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008870:Microtubules / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; C115084:Pard3 protein, mouse
keywords: EMT; centrosome; cytoskeleton; intercellular junctions; micropatterning; microtubule; migration; polarity; stathmin