Key result
Zebrafish with a novel nrg1 null allele exhibited reduced survivorship, structural and functional cardiac defects, and missing long axons on the ventricle surface during development.
Why the study?
Does nrg1 null mutation affect cardiac structural and functional parameters and nerve plexus formation in a zebrafish model?
Does nrg1 null mutation affect cardiac structural and functional parameters and nerve plexus formation in a zebrafish model?
Neuregulin-1 is essential for establishing the cardiac nerve plexus, and its absence leads to deficits in cardiac maturation, function, and survival in a zebrafish model.
nrg1 mutation disrupts zebrafish cardiac nerve plexus and function; hypothesis-generating for NRG1 in human cardiomyopathy, no practice change.
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.
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Brown et al. (2017) studied Cardiac maturation and nerve plexus formation. nrg1 null allele vs. Wild-type (implied) was evaluated on Cardiac structural and functional parameters, survivorship, and nerve plexus formation. Zebrafish with a novel nrg1 null allele exhibited reduced survivorship, structural and functional cardiac defects, and missing long axons on the ventricle surface during development.
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