PUBLICATION
Regulation of cardiomyocyte behavior in zebrafish trabeculation by Neuregulin 2a signaling
- Authors
- Rasouli, S.J., Stainier, D.Y.R.
- ID
- ZDB-PUB-170510-5
- Date
- 2017
- Source
- Nature communications 8: 15281 (Journal)
- Registered Authors
- Stainier, Didier
- Keywords
- Cell proliferation, Cell signalling, Development, Super-resolution microscopy
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Coronary Circulation
- Embryo, Nonmammalian/metabolism
- Heart Atria/cytology
- Heart Atria/embryology
- Heart Ventricles/embryology
- Heart Ventricles/metabolism
- Larva/growth & development
- Larva/metabolism
- Mutation/genetics
- Myocytes, Cardiac/metabolism*
- Organogenesis*
- Recombinant Fusion Proteins/metabolism
- Signal Transduction*
- Zebrafish/embryology
- Zebrafish/metabolism*
- Zebrafish Proteins/metabolism*
- PubMed
- 28485381 Full text @ Nat. Commun.
Citation
Rasouli, S.J., Stainier, D.Y.R. (2017) Regulation of cardiomyocyte behavior in zebrafish trabeculation by Neuregulin 2a signaling. Nature communications. 8:15281.
Abstract
Trabeculation is crucial for cardiac muscle growth in vertebrates. This process requires the Erbb2/4 ligand Neuregulin (Nrg), secreted by the endocardium, as well as blood flow/cardiac contractility. Here, we address two fundamental, yet unresolved, questions about cardiac trabeculation: why does it initially occur in the ventricle and not the atrium, and how is it modulated by blood flow/contractility. Using loss-of-function approaches, we first show that zebrafish Nrg2a is required for trabeculation, and using a protein-trap line, find that it is expressed in both cardiac chambers albeit with different spatiotemporal patterns. Through gain-of-function experiments, we show that atrial cardiomyocytes can also respond to Nrg2a signalling, suggesting that the cardiac jelly, which remains prominent in the atrium, represents a barrier to Erbb2/4 activation. Furthermore, we find that blood flow/contractility is required for Nrg2a expression, and that while non-contractile hearts fail to trabeculate, non-contractile cardiomyocytes are also competent to respond to Nrg2a/Erbb2 signalling.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping