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
-
- Alleles
- Animals
- Animals, Genetically Modified
- Base Sequence
- CRISPR-Cas Systems
- Electrocardiography
- Embryo, Nonmammalian
- ErbB Receptors/genetics
- ErbB Receptors/metabolism
- Gene Editing
- Gene Expression Regulation, Developmental*
- Heart/growth & development
- Heart/innervation*
- Larva/growth & development
- Larva/metabolism
- Locomotion/physiology
- Longevity/genetics*
- Myocytes, Cardiac/metabolism
- Myocytes, Cardiac/pathology
- Neuregulin-1/deficiency
- Neuregulin-1/genetics*
- Neurogenesis/genetics
- Organogenesis/genetics
- RNA, Messenger/genetics*
- RNA, Messenger/metabolism
- Zebrafish/genetics*
- Zebrafish/growth & development
- Zebrafish/metabolism
- PubMed
- 29265764 Full text @ J. Cell. Mol. Med.
Citation
Brown, D., Samsa, L.A., Ito, C., Ma, H., Batres, K., Arnaout, R., Qian, L., Liu, J. (2017) Neuregulin-1 is essential for nerve plexus formation during cardiac maturation. Journal of Cellular and Molecular Medicine. 22(3):2007-2017.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping