PUBLICATION

Tension Creates an Endoreplication Wavefront that Leads Regeneration of Epicardial Tissue

Authors
Cao, J., Wang, J., Jackman, C.P., Cox, A.H., Trembley, M.A., Balowski, J.J., Cox, B.D., De Simone, A., Dickson, A.L., Di Talia, S., Small, E.M., Kiehart, D.P., Bursac, N., Poss, K.D.
ID
ZDB-PUB-170928-7
Date
2017
Source
Developmental Cell   42: 600-615.e4 (Journal)
Registered Authors
Balowski, Joseph, Cao, Jingli, Cox, Ben, Dickson, Amy, Poss, Kenneth D., Wang, Jinhu
Keywords
endoreplication, epicardium, heart, mechanical tension, polyploidy, regeneration, zebrafish
MeSH Terms
  • Animals
  • Biomechanical Phenomena
  • Cell Movement
  • Endoreduplication*
  • Giant Cells/pathology
  • Hypertrophy
  • Mice, Inbred C57BL
  • Mitosis
  • Pericardium/physiology*
  • Polyploidy
  • Regeneration*
  • Zebrafish
PubMed
28950101 Full text @ Dev. Cell
Abstract
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.
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