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

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Date
2015-04-01
Authors
Gemberling, Matthew
Karra, Ravi
Dickson, Amy L
Poss, Kenneth D
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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 article
Subject
Neuregulin1
cardiac 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/10161/9718
Published Version (Please cite this version)
10.7554/eLife.05871
Publication 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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Scholars@Duke

Karra

Ravi Karra

Associate Professor of Medicine
Poss

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
Alphabetical list of authors with Scholars@Duke profiles.
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