ZFIN ID: ZDB-PUB-150811-9
Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration
Mahmoud, A.I., O'Meara, C.C., Gemberling, M., Zhao, L., Bryant, D.M., Zheng, R., Gannon, J.B., Cai, L., Choi, W.Y., Egnaczyk, G.F., Burns, C.E., Burns, C.G., MacRae, C.A., Poss, K.D., Lee, R.T.
Date: 2015
Source: Developmental Cell   34(4): 387-99 (Journal)
Registered Authors: Burns (Erter), Caroline, Burns, Geoff, Choi, Wen-Yee, Egnaczyk, Greg, Gemberling, Matt, MacRae, Calum A., Poss, Kenneth D., Zhao, Long
Keywords: none
Microarrays: GEO:GSE69775
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Animals, Newborn
  • Cell Proliferation/drug effects
  • Cholinergic Neurons/physiology*
  • Denervation
  • Gene Expression Regulation/drug effects
  • Heart/innervation*
  • Heart/physiology*
  • Immunity/drug effects
  • Immunity/genetics
  • Inflammation/genetics
  • Mice
  • Models, Biological
  • Molecular Sequence Data
  • Myocytes, Cardiac/cytology*
  • Nerve Growth Factor/pharmacology
  • Neuregulin-1/pharmacology
  • Regeneration*/drug effects
  • Synaptic Transmission/drug effects
  • Vagotomy
  • Zebrafish
PubMed: 26256209 Full text @ Dev. Cell
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 revealedĀ a blunted inflammatory and immune response following injury. These findings demonstrate that nerve function is required for both zebrafish and mouse heart regeneration.