Epithelial repair is a two-stage process driven first by dying cells and then by their neighbours.
Epithelial cells maintain an essential barrier despite continuously undergoing mitosis and apoptosis. Biological and biophysical mechanisms have evolved to remove dying cells while maintaining that barrier. Cell extrusion is thought to be driven by a multicellular filamentous actin ring formed by neighbouring cells, the contraction of which provides the mechanical force for extrusion, with little or no contribution from the dying cell. Here, we use live confocal imaging, providing time-resolved three-dimensional observations of actomyosin dynamics, to reveal new mechanical roles for dying cells in their own extrusion from monolayers. Based on our observations, the clearance of dying cells can be subdivided into two stages. The first, previously unidentified, stage is driven by the dying cell, which exerts tension on its neighbours through the action of a cortical contractile F-actin and myosin ring at the cell apex. The second stage, consistent with previous studies, is driven by a multicellular F-actin ring in the neighbouring cells that moves from the apical to the basal plane to extrude the dying cell. Crucially, these data reinstate the dying cell as an active physical participant in cell extrusion.
CoMPLEX PhD program, University College London, Gower Street, London WC1E 6BT, UK.
Dorothy
D
Kuipers
Aida
A
Mehonic
Mihoko
M
Kajita
Loïc
L
Peter
Yasuyuki
Y
Fujita
Tom
T
Duke
Guillaume
G
Charras
Jonathan E
JE
Gale
D000205:Actomyosin / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D002463:Cell Membrane Permeability; D016764:Cell Polarity; D048430:Cell Shape; D004285:Dogs; D004848:Epithelium / Q000502:physiology; D061985:Madin Darby Canine Kidney Cells; D021381:Protein Transport; D059008:Time-Lapse Imaging; D014945:Wound Healing
D000205:Actomyosin
Actin dynamics; Apoptosis; Cell death; Epithelia; Extrusion; Myosin; RhoGTPase