Tissue-tissue interactions during morphogenesis of the outflow tract

Abstract

The heart forms as a linear heart tube that loops and septates to produce a mature four-chambered structure. The single vessel emerging from the embryonic heart, the truncus arteriosus, divides into the aorta and the pulmonary artery as part of this septation process, and a series of additional morphogenetic events result in the proper alignment and orientation of the cardiac outflow tract. Recent evidence indicates that this process involves the complex interactions of multiple cell types including primary and secondary heart fields, neural crest, pharyngeal mesenchyme, endoderm, and endothelium. Among the many signals that mediate tissue-tissue interactions during the formation of the outflow tract, we have focused on the role of the Notch signaling pathway. Here, we focus on recent advances in our understanding of Notch-mediated regulation of cardiac development with specific attention to the formation of the cardiac outflow tract.

Fig. 1

Tissue–tissue interactions during outflow tract development. The model depicts second heart field myocardium, endothelium undergoing EMT, and cardiac neural crest. Jagged1/Notch signaling in the second heart field is proposed to stimulate Fgf8, which functions within the second heart field to regulate downstream cascades including Bmp4, which in turn signals to endothelium and neural crest. Reprinted with permission from the Journal of Clinical Investigation [13]