Tension Creates an Endoreplication Wavefront that Leads Regeneration of Epicardial Tissue

Publication date: 25 September 2017
Source:Developmental Cell, Volume 42, Issue 6
Author(s): Jingli Cao, Jinhu Wang, Christopher P. Jackman, Amanda H. Cox, Michael A. Trembley, Joseph J. Balowski, Ben D. Cox, Alessandro De Simone, Amy L. Dickson, Stefano Di Talia, Eric M. Small, Daniel P. Kiehart, Nenad Bursac, Kenneth D. Poss
Mechanisms that control cell-cycle dynamics during tissue regeneration require elucidation. Here we find in zebrafish that regeneration of the epicardium, the mesothelial covering of the heart, is mediated by two phenotypically distinct epicardial cell subpopulations. These include a front of large, multinucleate leader cells, trailed by follower cells that divide to produce small, mononucleate daughters. By using live imaging of cell-cycle dynamics, we show that leader cells form by spatiotemporally regulated endoreplication, caused primarily by cytokinesis failure. Leader cells display greater velocities and mechanical tension within the epicardial tissue sheet, and experimentally induced tension anisotropy stimulates ectopic endoreplication. Unbalancing epicardial cell-cycle dynamics with chemical modulators indicated autonomous regenerative capacity in both leader and follower cells, with leaders displaying an enhanced capacity for surface coverage. Our findings provide evidence that mechanical tension can regulate cell-cycle dynamics in regenerating tissue, stratifying the source cell features to improve repair.

Graphical abstract

Teaser

Cao et al. devise genetic tools and live-imaging platforms in zebrafish to visualize cell-cycle dynamics during regeneration of the epicardial tissue that covers the heart. They uncover evidence that differences in mechanical tension within the tissue sheet create distinct zones of endoreplicating and dividing cells that enable regeneration.


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