Dependence of cardiac trabeculation on neuregulin signaling and blood flow in zebrafish.
Maturation of the developing heart requires the structural elaboration of the embryonic ventricle through the process of trabeculation. Trabeculae form as the ventricular myocardium protrudes into the lumen of the chamber, thereby increasing muscle mass and altering functional output. Little is understood about the cellular basis for trabeculation and its genetic regulation. Here, we establish the utility of the zebrafish embryo for the analysis of the mechanisms driving trabeculation. In zebrafish, we can follow trabeculation in four dimensions and define morphologically discrete stages for the initiation, propagation, and network elaboration that form the ventricular trabeculae. We find that Neuregulin/ErbB signaling is required for the initial protrusion of the myocardium into the ventricular lumen. Additionally, we demonstrate that optimal blood flow through the ventricle is important for the advancement of trabeculation. Thus, our results indicate that the zebrafish provides a valuable model for investigating possible causes of congenital defects in trabeculation.
Developmental Genetics Program and Department of Cell Biology, Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York, USA.
Courtney
C
Peshkovsky
Ronald
R
Totong
Deborah
D
Yelon
D000818:Animals; D006352:Heart Ventricles / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism*; D008953:Models, Anatomic; D020880:Neuregulins / Q000378:metabolism*; D018739:Oncogene Proteins v-erbB / Q000235:genetics / Q000378:metabolism; D038081:Organogenesis / Q000502:physiology; D012039:Regional Blood Flow; D015398:Signal Transduction / Q000502:physiology*; D019076:Transgenes; D015027:Zebrafish / Q000033:anatomy & histology* / Q000196:embryology* / Q000378:metabolism
D020880:Neuregulins; D018739:Oncogene Proteins v-erbB