Cellular crowding influences extrusion and proliferation to facilitate epithelial tissue repair

Molecular Biology of the Cell
Jovany J FrancoGeorge T Eisenhoffer

Abstract

Epithelial wound healing requires a complex orchestration of cellular rearrangements and movements to restore tissue architecture and function after injury. While it is well known that mechanical forces can affect tissue morphogenesis and patterning, how the biophysical cues generated after injury influence cellular behaviors during tissue repair is not well understood. Using time-lapse confocal imaging of epithelial tissues in living zebrafish larvae, we provide evidence that localized increases in cellular crowding during wound closure promote the extrusion of nonapoptotic cells via mechanically regulated stretch-activated ion channels (SACs). Directed cell migration toward the injury site promoted rapid changes in cell number and generated shifts in tension at cellular interfaces over long spatial distances. Perturbation of SAC activity resulted in failed extrusion and increased proliferation in crowded areas of the tissue. Together, we conclude that localized cell number plays a key role in dictating cellular behaviors that facilitate wound closure and tissue repair.

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Citations

Jul 20, 2019·Molecular Biology of the Cell·Dennis E Discher
Jul 5, 2021·Cells & Development·Sriivatsan G RajanAnkur Saxena

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Methods Mentioned

BETA
transgenic
amputation

Software Mentioned

PIVlab
Zen
Fiji ImageJ
MATLAB
Imaris
CellFIT
GraphPad Prism
ImageJ
Cellular Force Inference Toolkit
Bitplain Imaris

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