Community Action Needed: Please respond to the NIH RFI
ZFIN ID: ZDB-PUB-170510-5
Regulation of cardiomyocyte behavior in zebrafish trabeculation by Neuregulin 2a signaling
Rasouli, S.J., Stainier, D.Y.R.
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.
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.