Poelmann R E, Gittenberger-de Groot A C
Department of Anatomy and Embryology, Leiden University Medical Center, Wassenaarseweg 62, Leiden, 2300RC, The Netherlands.
Dev Biol. 1999 Mar 15;207(2):271-86. doi: 10.1006/dbio.1998.9166.
A well-described population of cardiac neural crest (NC) cells migrates toward the arterial pole of the embryonic heart and differentiates into various cell types, including smooth muscle cells of the pharyngeal arch arteries (but not the coronary arteries), cardiac ganglionic cells, and mesenchymal cells of the aortopulmonary septum. Using a replication-incompetent retrovirus containing 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 these cells might not only originate from the dorsal part of the posterior rhombencephalon, but also from the ventral part. These NC cells migrate to locations surrounding the prospective conduction system as well as to the atrioventricular (AV) cushions. Concerning the prospective conduction system, the tagged neural crest cells can be found in regions where the atrioventricular node area, the retroaortic root bundle, the bundle of His, the left and right bundle branches, and the right atrioventricular ring bundle are positioned. The last area connects the posteriorly located AV node area with the retroaortic root bundle, which receives its neural crest cells 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 detection. It is possible that the NC cells in the heart become anoikic and, as a consequence, fail to differentiate further and merely die. However, because of the perfect timing of the arrival of crest cells, their apoptosis, and a change in electrophysiological behavior of the heart, we postulate that neural crest cells play a role in the last phase of differentiation of the cardiac conduction system. Alternatively, the separation of the central conduction system from the surrounding working myocardium is mediated by apoptotic neural crest cells. As for the presence of NC cells in both the outflow tract and the AV cushions, followed by apoptosis, a function is assigned in the muscularization of both areas, resulting in proper septation of the outflow tract and of the AV region. Failure of normal neural crest development may not only play a role in cardiac outflow tract anomalies but also in inflow tract abnormalities, such as atrioventricular septal defects.
一类已被充分描述的心脏神经嵴（NC）细胞向胚胎心脏的动脉极迁移，并分化为多种细胞类型，包括咽弓动脉（而非冠状动脉）的平滑肌细胞、心脏神经节细胞以及主动脉肺动脉隔的间充质细胞。我们将携带报告基因LacZ的无复制能力逆转录病毒注入鸡胚的迁移神经嵴，结果显示另一类心脏神经嵴细胞通过静脉极进入心脏。基于我们目前的数据，我们不能排除这些细胞的前体可能不仅起源于后脑后部的背侧部分，还可能起源于腹侧部分的可能性。这些NC细胞迁移到预期传导系统周围以及房室（AV）垫的位置。关于预期传导系统，在房室结区域、主动脉后根束、希氏束、左右束支以及右房室环束所在的区域可以发现被标记的神经嵴细胞。最后一个区域将位于后方的房室结区域与主动脉后根束相连，主动脉后根束与形成主动脉肺动脉隔的细胞一起通过动脉极接收其神经嵴细胞。这些NC细胞很可能不会形成真正的传导系统，因为通过同时进行的TUNEL检测确定它们进入了凋亡途径。心脏中的NC细胞有可能变得失巢凋亡，结果无法进一步分化而仅仅死亡。然而，由于嵴细胞到达的完美时机、它们的凋亡以及心脏电生理行为的改变，我们推测神经嵴细胞在心脏传导系统分化的最后阶段发挥作用。或者，中枢传导系统与周围工作心肌的分离是由凋亡的神经嵴细胞介导的。至于在流出道和房室垫中均存在NC细胞，随后发生凋亡，这被认为在这两个区域的肌化过程中发挥作用，从而导致流出道和房室区域的正常分隔。正常神经嵴发育的失败不仅可能在心脏流出道异常中起作用，还可能在流入道异常如房室间隔缺损中起作用。
