Disruption of<i>pdgfra</i>alters endocardial and myocardial fusion during zebrafish cardiac assembly

Abstract

Cardiac development in vertebrates is a finely tuned process regulated by a set of conserved signaling pathways. Perturbations of these processes are often associated with congenital cardiac malformations. Platelet-derived growth factor receptor α (PDGFRα) is a highly conserved tyrosine kinase receptor, which is essential for development and organogenesis. Disruption of <i>Pdgfrα</i> function in murine models is embryonic lethal due to severe cardiovascular defects, suggesting a role in cardiac development, thus necessitating the use of alternative models to explore its precise function. In this study, we generated a zebrafish <i>pdgfra</i> mutant line by gene trapping, in which the Pdgfra protein is truncated and fused with mRFP (Pdgfra-mRFP). Our results demonstrate that <i>pdgfra</i> mutants have defects in cardiac morphology as a result of abnormal fusion of myocardial precursors. Expression analysis of the developing heart at later stages suggested that Pdgfra-mRFP is expressed in the endocardium. Further examination of the endocardium in <i>pdgfra</i> mutants revealed defective endocardial migration to the midline, where cardiac fusion eventually occurs. Together, our data suggests that <i>pdgfra</i> is required for proper medial migration of both endocardial and myocardial precursors, an essential step required for cardiac assembly and development.