Cellular Crowding Influences Extrusion and Proliferation to Facilitate Epithelial Tissue Repair
Overview
Molecular Biology
Affiliations
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.
Hippee C, Durnell L, Kaufman J, Murray E, Singh B, Sinn P J Virol. 2025; 99(2):e0122024.
PMID: 39791903 PMC: 11852777. DOI: 10.1128/jvi.01220-24.
Epithelial cell-cell interactions in an overcrowded environment: jamming or live cell extrusion.
Pajic-Lijakovic I, Milivojevic M, McClintock P J Biol Eng. 2024; 18(1):47.
PMID: 39237992 PMC: 11378474. DOI: 10.1186/s13036-024-00442-3.
Cell extrusion - a novel mechanism driving neural crest cell delamination.
Moore E, Zhao R, McKinney M, Yi K, Wood C, Trainor P bioRxiv. 2024; .
PMID: 38559094 PMC: 10979875. DOI: 10.1101/2024.03.09.584232.
Han I, Hua J, White J, OConnor J, Nassar L, Tro K Mol Biol Cell. 2024; 35(5):ar66.
PMID: 38536445 PMC: 11151093. DOI: 10.1091/mbc.E23-05-0204.
Engineering tools for quantifying and manipulating forces in epithelia.
Dow L, Parmar T, Marchetti M, Pruitt B Biophys Rev (Melville). 2024; 4(2):021303.
PMID: 38510344 PMC: 10903508. DOI: 10.1063/5.0142537.