PUBLICATION
Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration
- Authors
- 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.
- ID
- ZDB-PUB-150811-9
- 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
- Datasets
- GEO:GSE69775
- MeSH Terms
-
- Neuregulin-1/pharmacology
- Molecular Sequence Data
- Animals, Genetically Modified
- Cell Proliferation/drug effects
- Vagotomy
- Models, Biological
- Mice
- Nerve Growth Factor/pharmacology
- Myocytes, Cardiac/cytology*
- Gene Expression Regulation/drug effects
- Synaptic Transmission/drug effects
- Animals, Newborn
- Zebrafish
- Inflammation/genetics
- Regeneration*/drug effects
- Denervation
- Immunity/drug effects
- Immunity/genetics
- Animals
- Heart/innervation*
- Heart/physiology*
- Cholinergic Neurons/physiology*
- PubMed
- 26256209 Full text @ Dev. Cell
Citation
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. (2015) Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration. Developmental Cell. 34(4):387-99.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping