title: In vivo collective cell migration requires an LPAR2-dependent increase in tissue fluidity.
abstract: Collective cell migration (CCM) and epithelial-mesenchymal transition (EMT) are common to cancer and morphogenesis, and are often considered to be mutually exclusive in spite of the fact that many cancer and embryonic cells that have gone through EMT still cooperate to migrate collectively. Here we use neural crest (NC) cells to address the question of how cells that have down-regulated cell-cell adhesions can migrate collectively. NC cell dissociation relies on a qualitative and quantitative change of the cadherin repertoire. We found that the level of cell-cell adhesion is precisely regulated by internalization of N-cadherin downstream of lysophosphatidic acid (LPA) receptor 2. Rather than promoting the generation of single, fully mesenchymal cells, this reduction of membrane N-cadherin only triggers a partial mesenchymal phenotype. This intermediate phenotype is characterized by an increase in tissue fluidity akin to a solid-like-to-fluid-like transition. This change of plasticity allows cells to migrate under physical constraints without abolishing cell cooperation required for collectiveness.
authors.affiliation: Cell and Developmental Biology Department, University College London, London WC1E 6BT, England, UK Department of Molecular Medicine and Biochemistry, Akita University Graduate School of Medicine and Faculty of Medicine, Akita City, Akita 010-8543, Japan.
authors.forename: Sei
authors.initials: S
authors.lastname: Kuriyama
authors.affiliation: Cell and Developmental Biology Department, University College London, London WC1E 6BT, England, UK.
authors.forename: Eric
authors.initials: E
authors.lastname: Theveneau
authors.affiliation: London Centre for Nanotechnology, University College London, London WC1H 0AH, England, UK.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Benedetto
authors.affiliation: Randall Division of Cell and Molecular Biophysics, Kings College London, London SE11UL, England, UK.
authors.forename: Maddy
authors.initials: M
authors.lastname: Parsons
authors.affiliation: Department of Molecular Medicine and Biochemistry, Akita University Graduate School of Medicine and Faculty of Medicine, Akita City, Akita 010-8543, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Cell and Developmental Biology Department, University College London, London WC1E 6BT, England, UK London Centre for Nanotechnology, University College London, London WC1H 0AH, England, UK.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Charras
authors.affiliation: Engineering Department, Mechanics and Materials Division, Cambridge University, Cambridge CB2 1PZ, England, UK.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Kabla
authors.affiliation: Cell and Developmental Biology Department, University College London, London WC1E 6BT, England, UK r.mayor@ucl.ac.uk.
authors.forename: Roberto
authors.initials: R
authors.lastname: Mayor
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D002633:Chemotaxis; D007365:Intercellular Junctions / Q000378:metabolism; D008246:Lysophospholipids / Q000502:physiology; D009432:Neural Crest / Q000166:cytology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism*; D015398:Signal Transduction; D029867:Xenopus Proteins / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D015820:Cadherins; D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; D029867:Xenopus Proteins; C032881:lysophosphatidic acid