PUBLICATION

Neuregulin-1 is essential for nerve plexus formation during cardiac maturation

Authors
Brown, D., Samsa, L.A., Ito, C., Ma, H., Batres, K., Arnaout, R., Qian, L., Liu, J.
ID
ZDB-PUB-171222-9
Date
2017
Source
Journal of Cellular and Molecular Medicine   22(3): 2007-2017 (Journal)
Registered Authors
Brown, Daniel, Ito, Cade, Liu, Jiandong, Ma, Hong, Samsa, Leigh Ann
Keywords
cardiac innervation, cardiac maturation, neuregulin-1, zebrafish
MeSH Terms
  • Neurogenesis/genetics
  • Electrocardiography
  • Longevity/genetics*
  • CRISPR-Cas Systems
  • ErbB Receptors/genetics
  • ErbB Receptors/metabolism
  • Larva/growth & development
  • Larva/metabolism
  • Gene Expression Regulation, Developmental*
  • Base Sequence
  • Alleles
  • Animals, Genetically Modified
  • Locomotion/physiology
  • Heart/growth & development
  • Heart/innervation*
  • Embryo, Nonmammalian
  • Neuregulin-1/deficiency
  • Neuregulin-1/genetics*
  • Animals
  • Gene Editing
  • Zebrafish/genetics*
  • Zebrafish/growth & development
  • Zebrafish/metabolism
  • RNA, Messenger/genetics*
  • RNA, Messenger/metabolism
  • Myocytes, Cardiac/metabolism
  • Myocytes, Cardiac/pathology
  • Organogenesis/genetics
(all 28)
PubMed
29265764 Full text @ J. Cell. Mol. Med.
Abstract
The Neuregulin-1 (Nrg1)/ErbB pathway plays multiple, critical roles in early cardiac and nervous system development and has been implicated in both heart and nerve repair processes. However, the early embryonic lethality of mouse Nrg1 mutants precludes an analysis of Nrg1's function in later cardiac development and homeostasis. In this study, we generated a novel nrg1 null allele targeting all known isoforms of nrg1 in zebrafish and examined cardiac structural and functional parameters throughout development. We found that zebrafish nrg1 mutants instead survived until young adult stages when they exhibited reduced survivorship. This coincided with structural and functional defects in the developing juvenile and young adult hearts, as demonstrated by reduced intracardiac myocardial density, cardiomyocyte cell number, swimming performance and dysregulated heartbeat. Interestingly, nrg1 mutant hearts were missing long axons on the ventricle surface by standard length (SL) 5 mm, which preceded juvenile and adult cardiac defects. Given that the autonomic nervous system normally exerts fine control of cardiac output through this nerve plexus, these data suggest that Nrg1 may play a critical role in establishing the cardiac nerve plexus such that inadequate innervation leads to deficits in cardiac maturation, function and survival.
Genes / Markers
Figures
Figure Gallery (5 images)
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Expression
No data available
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
f2TgTransgenic Insertion
    nc26
      Small Deletion
      nc27
        Small Deletion
        s883TgTransgenic Insertion
          z26
            Point Mutation
            1 - 5 of 5
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            Human Disease / Model
            No data available
            Sequence Targeting Reagents
            Target Reagent Reagent Type
            nrg1CRISPR2-nrg1CRISPR
            1 - 1 of 1
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            Fish
            Antibodies
            No data available
            Orthology
            No data available
            Engineered Foreign Genes
            Marker Marker Type Name
            DsRed2EFGDsRed2
            EGFPEFGEGFP
            1 - 2 of 2
            Show
            Mapping
            No data available