title: Regional-specific alterations in cell-cell junctions, cytoskeletal networks and myosin-mediated mechanical cues coordinate collectivity of movement of epithelial cells in response to injury.
abstract: This study investigates how epithelial cells moving together function to coordinate their collective movement to repair a wound. Using a lens ex vivo mock cataract surgery model we show that region-specific reorganization of cell-cell junctions, cytoskeletal networks and myosin function along apical and basal domains of an epithelium mediates the process of collective migration. An apical junctional complex composed of N-cadherin/ZO-1/myosin II linked to a cortical actin cytoskeleton network maintains integrity of the tissue during the healing process. These cells' basal domains often preceded their apical domains in the direction of movement, where an atypical N-cadherin/ZO-1 junction, linked to an actin stress fiber network rich in phosphomyosin, was prominent in cryptic lamellipodia. These junctions joined the protruding forward-moving lamellipodia to the back end of the cell moving directly in front of it. These were the only junctions detected in cryptic lamellipodia of lens epithelia migrating in response to wounding that could transmit the protrusive forces that drive collective movement. Both integrity of the epithelium and ability to effectively heal the wound was found to depend on myosin mechanical cues.
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, United States; Wills Vision Research Center at Jefferson, Philadelphia, PA 19107, United States.
authors.forename: A S
authors.initials: AS
authors.lastname: Menko
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, United States.
authors.forename: B M
authors.initials: BM
authors.lastname: Bleaken
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, United States; Wills Vision Research Center at Jefferson, Philadelphia, PA 19107, United States. Electronic address: janice.l.walker@jefferson.edu.
authors.forename: J L
authors.initials: JL
authors.lastname: Walker
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000502:physiology*; D002448:Cell Adhesion; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D003599:Cytoskeleton / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology*; D007365:Intercellular Junctions / Q000502:physiology*; D007908:Lens, Crystalline / Q000166:cytology / Q000293:injuries* / Q000502:physiology; D008962:Models, Theoretical; D009218:Myosins / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology
chemical_list: D009218:Myosins
keywords: Cadherin; Cell–cell junctions; Collective migration; Injury–repair; Lens; Myosin II; Sheet movement; Wound healing