Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration.

Journal Article (Journal Article)

Some organisms, such as adult zebrafish and newborn mice, have the capacity to regenerate heart tissue following injury. Unraveling the mechanisms of heart regeneration is fundamental to understanding why regeneration fails in adult humans. Numerous studies have revealed that nerves are crucial for organ regeneration, thus we aimed to determine whether nerves guide heart regeneration. Here, we show using transgenic zebrafish that inhibition of cardiac innervation leads to reduction of myocyte proliferation following injury. Specifically, pharmacological inhibition of cholinergic nerve function reduces cardiomyocyte proliferation in the injured hearts of both zebrafish and neonatal mice. Direct mechanical denervation impairs heart regeneration in neonatal mice, which was rescued by the administration of neuregulin 1 (NRG1) and nerve growth factor (NGF) recombinant proteins. Transcriptional analysis of mechanically denervated hearts revealed a blunted inflammatory and immune response following injury. These findings demonstrate that nerve function is required for both zebrafish and mouse heart regeneration.

Full Text

Duke Authors

Cited Authors

  • Mahmoud, AI; O'Meara, CC; Gemberling, M; Zhao, L; Bryant, DM; Zheng, R; Gannon, JB; Cai, L; Choi, W-Y; Egnaczyk, GF; Burns, CE; Burns, CG; MacRae, CA; Poss, KD; Lee, RT

Published Date

  • August 24, 2015

Published In

Volume / Issue

  • 34 / 4

Start / End Page

  • 387 - 399

PubMed ID

  • 26256209

Pubmed Central ID

  • PMC4550513

Electronic International Standard Serial Number (EISSN)

  • 1878-1551

Digital Object Identifier (DOI)

  • 10.1016/j.devcel.2015.06.017


  • eng

Conference Location

  • United States