PUBLICATION

Migration of cardiomyocytes is essential for heart regeneration in zebrafish

Authors
Itou, J., Oishi, I., Kawakami, H., Glass, T.J., Richter, J., Johnson, A., Lund, T.C., and Kawakami, Y.
ID
ZDB-PUB-121012-29
Date
2012
Source
Development (Cambridge, England)   139(22): 4133-4142 (Journal)
Registered Authors
Kawakami, Hiroko, Lund, Troy
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Cell Movement
  • Cell Proliferation
  • Chemokine CXCL12/biosynthesis*
  • Chemokine CXCL12/genetics
  • Heart/physiology*
  • Heart Injuries/physiopathology
  • Heart Ventricles
  • Myocardium/metabolism
  • Myocytes, Cardiac/physiology*
  • Receptors, CXCR4/biosynthesis*
  • Receptors, CXCR4/genetics
  • Regeneration*
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
  • Zebrafish*/physiology
  • Zebrafish Proteins/biosynthesis*
  • Zebrafish Proteins/genetics
PubMed
23034636 Full text @ Development
Abstract

Adult zebrafish possess a significant ability to regenerate injured heart tissue through proliferation of pre-existing cardiomyocytes, which contrasts with the inability of mammals to do so after the immediate postnatal period. Zebrafish therefore provide a model system in which to study how an injured heart can be repaired. However, it remains unknown what important processes cardiomyocytes are involved in other than partial de-differentiation and proliferation. Here we show that migration of cardiomyocytes to the injury site is essential for heart regeneration. Ventricular amputation induced expression of cxcl12a and cxcr4b, genes encoding a chemokine ligand and its receptor. We found that cxcl12a was expressed in the epicardial tissue and that Cxcr4 was expressed in cardiomyocytes. We show that pharmacological blocking of Cxcr4 function as well as genetic loss of cxcr4b function causes failure to regenerate the heart after ventricular resection. Cardiomyocyte proliferation was not affected but a large portion of proliferating cardiomyocytes remained localized outside the injury site. A photoconvertible fluorescent reporter-based cardiomyocyte-tracing assay demonstrates that cardiomyocytes migrated into the injury site in control hearts but that migration was inhibited in the Cxcr4-blocked hearts. By contrast, the epicardial cells and vascular endothelial cells were not affected by blocking Cxcr4 function. Our data show that the migration of cardiomyocytes into the injury site is regulated independently of proliferation, and that coordination of both processes is necessary for heart regeneration.

Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping