Tension Creates an Endoreplication Wavefront that Leads Regeneration of Epicardial Tissue.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Cao, J; Wang, J; Jackman, CP; Cox, AH; Trembley, MA; Balowski, JJ; Cox, BD; De Simone, A; Dickson, AL; Di Talia, S; Small, EM; Kiehart, DP; Bursac, N; Poss, KD

Published Date

  • September 25, 2017

Published In

Volume / Issue

  • 42 / 6

Start / End Page

  • 600 - 615.e4

PubMed ID

  • 28950101

Pubmed Central ID

  • PMC5645043

Electronic International Standard Serial Number (EISSN)

  • 1878-1551

Digital Object Identifier (DOI)

  • 10.1016/j.devcel.2017.08.024


  • eng

Conference Location

  • United States