Neural Crest Derived Cardiomyocytes Regulate Cardiac Trabeculation and Adult Heart Function.

Abstract

The cardiac neural crest arise from the multi‐potent, migratory neural crest cell population and contribute to cardiovascular development, including contributions to cardiac endothelium and myocardium, formation of the great vessels and their valves, as well as septation of the chambers. However, very little is known about the neural crest contribution to the myocardium. This study aims to selectively decipher the function of the neural crest derived cardiomyocytes (NC‐Cms) without the confounding roles of the contributions of neural crest to other tissues, including endocardium. Zebrafish provide a unique genetic model to study this population because of their developmental transparency and they have a relatively large neural crest contribution of NC‐Cms compared to mammals. By creating Zebrafish transgenic lines that both lineage label and allow for ablation of only NC‐Cms, we find that the embryonic NC‐Cms arrive early in zebrafish heart development, makeup ~10% of the embryonic cardiomyocyte population and are steady state by two days post fertilization (2dpf). A majority of this contribution is to the ventricle in a discrete pattern around the apex of the ventricle. To test the function of NC‐Cms during heart development, we genetically ablated them during their early stages (up to 2dpf) and then observed heart development and phenotype up to 14dpf and into adulthood. Surprisingly embryonic ablation of the NC‐Cms was largely dispensable for heart development with a non‐lethal but significant defect in patterning of ventricle trabeculation. Importantly, embryonic ablation of NC‐Cms yielded adults with hypertrabeculated hearts and impaired performance in cardiac stress tests. We investigated the relation of the NC‐Cms to known Notch and Neuregulin effectors of embryonic trabeculation and speculate on their mechanistic regulation of this pathway. These results present a new model of human left ventricular non‐compaction or hypertrabeculation cardiomyopathy, and adult heart failure. Importantly these results demonstrate how a subtle and relatively minor developmental cell population can have detrimental effects on adult cardiac function.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.