Open AccessNeuregulin‐1 is essential for nerve plexus formation during cardiac maturation
Author(s) -
Brown Daniel,
Samsa Leigh Ann,
Ito Cade,
Ma Hong,
Batres Karla,
Arnaout Rima,
Qian Li,
Liu Jiandong
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13408
Subject(s) - neuregulin 1 , zebrafish , cardiac function curve , biology , erbb , heart development , heartbeat , plexus , ventricle , intracardiac injection , nervous system , neuroscience , endocrinology , medicine , anatomy , microbiology and biotechnology , heart failure , embryonic stem cell , signal transduction , genetics , computer security , computer science , gene
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.