PUBLICATION

Retinoic Acid production by endocardium and epicardium is an injury response essential for zebrafish heart regeneration

Authors
Kikuchi, K., Holdway, J.E., Major, R.J., Blum, N., Dahn, R.D., Begemann, G., and Poss, K.D.
ID
ZDB-PUB-110328-3
Date
2011
Source
Developmental Cell   20(3): 397-404 (Journal)
Registered Authors
Begemann, Gerrit, Holdway, Jennifer, Kikuchi, Kazu, Major, Bob, Poss, Kenneth D.
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Biological Evolution
  • Cell Proliferation
  • Endocardium/cytology
  • Endocardium/injuries
  • Endocardium/metabolism*
  • Heart/anatomy & histology
  • Heart/physiology*
  • Mice
  • Molecular Sequence Data
  • Myocytes, Cardiac/cytology
  • Myocytes, Cardiac/physiology
  • Pericardium/cytology
  • Pericardium/injuries
  • Pericardium/metabolism*
  • Regeneration/physiology*
  • Retinal Dehydrogenase/genetics
  • Retinal Dehydrogenase/metabolism
  • Signal Transduction/physiology
  • Tretinoin/metabolism*
  • Zebrafish/anatomy & histology
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
21397850 Full text @ Dev. Cell
Abstract
Zebrafish heart regeneration occurs through the activation of cardiomyocyte proliferation in areas of trauma. Here, we show that within 3 hr of ventricular injury, the entire endocardium undergoes morphological changes and induces expression of the retinoic acid (RA)-synthesizing enzyme raldh2. By one day posttrauma, raldh2 expression becomes localized to endocardial cells at the injury site, an area that is supplemented with raldh2-expressing epicardial cells as cardiogenesis begins. Induced transgenic inhibition of RA receptors or expression of an RA-degrading enzyme blocked regenerative cardiomyocyte proliferation. Injured hearts of the ancient fish Polypterus senegalus also induced and maintained robust endocardial and epicardial raldh2 expression coincident with cardiomyocyte proliferation, whereas poorly regenerative infarcted murine hearts did not. Our findings reveal that the endocardium is a dynamic, injury-responsive source of RA in zebrafish, and indicate key roles for endocardial and epicardial cells in targeting RA synthesis to damaged heart tissue and promoting cardiomyocyte proliferation.
Genes / Markers
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Figure Gallery
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes