Cardiac neural crest cells provide new insight into septation of the cardiac outflow tract: aortic sac to ventricular septal closure

Abstract

A great deal is unclear about the process of cardiac outflow septation. Much controversy exists regarding the precise details of tissue origins and movements of various components. The contribution of the cardiac neural crest to aorticopulmonary and distal truncal septation has been described; however, the distribution of the neural crest in the proximal outflow and heart is unknown. The present study describes the movement of cardiac neural crest cells from the caudal pharyngeal arches into the outflow tract and base of the heart during the period of outflow septation. Using quail-chick chimeras we found that the cardiac neural crest was distributed to all levels of the outflow tract and into the base of the heart. Septation of the outflow tract lumen occurred by two different processes that involved the cardiac neural crest directly. Cardiac neural crest cells were also distributed to regions of the outflow tract that correlated with sites of remodeling, such as the aortic sac as it was remodeled into the base of the ascending aorta and pulmonary trunk, the distal truncus that was patterned into the two semilunar valves and in the proximal conotruncus where muscularization of the ridges and septum occurred. Additionally, cardiac neural crest cells were found at the site of closure of the ventricular septum, in the wall of the pulmonary infundibulum, and transiently in the wall of the aortic vestibule. Contrary to current thinking, not all of the condensed mesenchyme in the outflow tract during septation was derived from neural crest.