PUBLICATION

Nrg1 is an injury-induced cardiomyocyte mitogen for the endogenous heart regeneration program in zebrafish

Authors
Gemberling, M., Karra, R., Dickson, A.L., Poss, K.D.
ID
ZDB-PUB-150402-3
Date
2015
Source
eLIFE   4: (Journal)
Registered Authors
Dickson, Amy, Gemberling, Matt, Karra, Ravi, Poss, Kenneth D.
Keywords
Neuregulin1, cardiac hyperplasia, cardiomyocyte, developmental biology, epicardium, heart regeneration, stem cells, zebrafish
MeSH Terms
  • Animals
  • Cardiomegaly/pathology
  • Cell Proliferation
  • Echocardiography
  • Heart/physiology*
  • Heart Ventricles/pathology
  • Hyperplasia
  • Mitogens/metabolism*
  • Myocardium/metabolism
  • Myocardium/pathology
  • Myocytes, Cardiac/metabolism
  • Myocytes, Cardiac/pathology
  • Neuregulin-1/metabolism*
  • Regeneration*
  • Signal Transduction
  • Zebrafish/physiology*
  • Zebrafish Proteins/metabolism*
PubMed
25830562 Full text @ Elife
Abstract
Heart regeneration is limited in adult mammals but occurs naturally in adult zebrafish through the activation of cardiomyocyte division. Several components of the cardiac injury microenvironment have been identified, yet no factor on its own is known to stimulate overt myocardial hyperplasia in a mature, uninjured animal. In this study, we find evidence that Neuregulin1 (Nrg1), previously shown to have mitogenic effects on mammalian cardiomyocytes, is sharply induced in perivascular cells after injury to the adult zebrafish heart. Inhibition of Erbb2, an Nrg1 co-receptor, disrupts cardiomyocyte proliferation in response to injury, whereas myocardial Nrg1 overexpression enhances this proliferation. In uninjured zebrafish, the reactivation of Nrg1 expression induces cardiomyocyte dedifferentiation, overt muscle hyperplasia, epicardial activation, increased vascularization, and causes cardiomegaly through persistent addition of wall myocardium. Our findings identify Nrg1 as a potent, induced mitogen for the endogenous adult heart regeneration program.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping