A subpopulation of apoptosis-prone cardiac neural crest cells targets to the venous pole: Multiple functions in heart development

A well-described population of cardiac neural crest (NC) cells migrates tow ard the arterial pole of the embryonic heart and differentiates into variou s cell types, including smooth muscle cells of the pharyngeal arch arteries (but not the coronary cardiac ganglionic cells, and mesenchymal cells of t he aortopulmonary septum. Using a replication-incompetent retrovirus contai ning the reporter gene LacZ, administered to the migratory neural crest of chicken embryos, we demonstrated another population of cardiac neural crest cells that employs the venous pole as entrance to the heart. On the basis of our present data we cannot exclude the possibility that precursors of th ese cells might not only originate from the dorsal part of the posterior rh ombencephalon, but also from the ventral part. These NC cells migrate to lo cations surrounding the prospective conduction system as well as to the atr ioventricular (AV) cushions. Concerning the prospective conduction system, the tagged neural crest cells can be found in regions where the atrioventri cular node area, the retroaortic root bundle, the bundle of His, the left a nd right bundle branches, and the right atrioventricular ring bundle are po sitioned. The last area connects the posteriorly located AV node area with the retroaortic root bundle, which receives its neural crest is through the arterial pole in concert with the cells giving rise to the aortopulmonary septum. The NC cells most probably do not form the conduction system proper , as they enter an apoptotic pathway as determined by concomitant TUNEL det ection. It is possible that the NC cells in the beast become anoikic and, a s a consequence, fail to differentiate and merely die. However, because of the perfect timing of the arrival of crest cells, their apoptosis, and a ch ange in electrophysiological behavior of the heart, we postulate that neura l crest cells play a role in the last phase of differentiation of the cardi ac conduction system. Alternatively, the separation of the central conducti on system from the surrounding working myocardium is mediated by apoptotic neural crest cells. As for the presence of NC cells in both the outflow tra ct the AV cushions, followed by apoptosis, a function is assigned in the mu scularization of both areas, resulting in proper septation of the outflow t ract and of the AV region. Failure of normal neural crest development may n ot only play a role in cardiac outflow tract anomalies but also in inflow t ract abnormalities, such as atrioventricular septal defects. (C) 1999 Acade mic Press.