PUBLICATION

Pulsatile contractions promote apoptotic cell extrusion in epithelial tissues

Authors

Atieh, Y., Wyatt, T., Zaske, A.M., Eisenhoffer, G.T.

ID

ZDB-PUB-210106-33

Date

2020

Source

Current biology : CB 31(6): 1129-1140.e4 (Journal)

Registered Authors

Atieh, Youmna, Eisenhoffer, George

Keywords

cell extrusion, epithelia, physical forces, tissue homeostasis, zebrafish

MeSH Terms

Epithelium
Epithelial Cells/cytology*
Zebrafish*/embryology
Apoptosis*
Actomyosin/metabolism
Animals
Myosins/metabolism

(all 7)

PubMed

33400921 Full text @ Curr. Biol.

Abstract

Extrusion is a mechanism used to eliminate unfit, excess, or dying cells from epithelial tissues. The initial events guiding which cells will be selectively extruded from the epithelium are not well understood. Here, we induced damage in a subset of epithelial cells in the developing zebrafish and used time-lapse imaging to examine cell and cytoskeletal dynamics leading to extrusion. We show that cell extrusion is preceded by actomyosin contractions that are pulsatile. Our data show that pulsatile contractions are induced by a junctional to medial re-localization of myosin. Analysis of cell area during contractions revealed that cells pulsing with the longest duration and highest amplitude undergo progressive area loss and extrude. Although pulses were driven by local increases in tension, damage to many cells promoted an overall decrease in the tensile state of the epithelium. We demonstrate that caspase activation leads to sphingosine-1-phosphate enrichment that controls both tissue tension and pulses to dictate areas of extrusion. These data suggest that the kinetics of pulsatile contractions define a key behavioral difference between extruding and non-extruding cells and are predictive of extrusion. Altogether, our study provides mechanistic insight into how localized changes in physical forces are coordinated to remove defective cells for homeostatic maintenance of living epithelial tissues.

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