PUBLICATION

Late developing cardiac lymphatic vasculature supports adult zebrafish heart function and regeneration

Authors
Harrison, M.R., Feng, X., Mo, G., Aguayo, A., Villafuerte, J., Yoshida, T., Pearson, C.A., Schulte-Merker, S., Lien, C.L.
ID
ZDB-PUB-191110-10
Date
2019
Source
eLIFE   8: (Journal)
Registered Authors
Harrison, Michael, Lien, Ching-Ling (Ellen), Schulte-Merker, Stefan
Keywords
developmental biology, regenerative medicine, stem cells, zebrafish
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Coronary Vessels/metabolism
  • Coronary Vessels/physiology
  • Gene Expression Regulation, Developmental
  • Heart/growth & development
  • Heart/physiology*
  • Humans
  • Lymphangiogenesis/genetics
  • Lymphangiogenesis/physiology*
  • Lymphatic Vessels/injuries
  • Lymphatic Vessels/metabolism
  • Lymphatic Vessels/physiopathology*
  • Mutation
  • Myocardium/metabolism*
  • Receptors, CXCR4/genetics
  • Receptors, CXCR4/metabolism
  • Regeneration/genetics
  • Regeneration/physiology
  • Vascular Endothelial Growth Factor C/genetics
  • Vascular Endothelial Growth Factor C/metabolism
  • Vascular Endothelial Growth Factor Receptor-3/genetics
  • Vascular Endothelial Growth Factor Receptor-3/metabolism
  • Zebrafish/genetics
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
31702553 Full text @ Elife
Abstract
The cardiac lymphatic vascular system and its potentially critical functions in heart patients have been largely underappreciated, in part due to a lack of experimentally accessible systems. We here demonstrate that cardiac lymphatic vessels develop in young adult zebrafish, using coronary arteries to guide their expansion down the ventricle. Mechanistically, we show that in cxcr4a mutants with defective coronary artery development, cardiac lymphatic vessels fail to expand onto the ventricle. In regenerating adult zebrafish hearts the lymphatic vasculature undergoes extensive lymphangiogenesis in response to a cryoinjury. A significant defect in reducing the scar size after cryoinjury is observed in zebrafish with impaired Vegfc/Vegfr3 signaling that fail to develop intact cardiac lymphatic vessels. These results suggest that the cardiac lymphatic system can influence the regenerative potential of the myocardium.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes