Nrg1 is an injury-induced cardiomyocyte mitogen for the endogenous heart regeneration program in zebrafish.
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.
Type
Journal articleSubject
Neuregulin1cardiac hyperplasia
cardiomyocyte
developmental biology
epicardium
heart regeneration
stem cells
zebrafish
Animals
Cardiomegaly
Cell Proliferation
Echocardiography
Heart
Heart Ventricles
Hyperplasia
Mitogens
Myocardium
Myocytes, Cardiac
Neuregulin-1
Regeneration
Signal Transduction
Zebrafish
Zebrafish Proteins
Permalink
https://hdl.handle.net/10161/9718Published Version (Please cite this version)
10.7554/eLife.05871Publication Info
Gemberling, Matthew; Karra, Ravi; Dickson, Amy L; & Poss, Kenneth D (2015). Nrg1 is an injury-induced cardiomyocyte mitogen for the endogenous heart regeneration
program in zebrafish. Elife, 4. 10.7554/eLife.05871. Retrieved from https://hdl.handle.net/10161/9718.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Ravi Karra
Associate Professor of Medicine
Kenneth Daniel Poss
James B. Duke Distinguished Professor of Regenerative Biology
Modeling disease in zebrafish Genetic approaches to organ regeneration Cardiac regeneration
Appendage regeneration Developmental biology
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