Bond Jacqueline, Sedmera David, Jourdan Jane, Zhang Yuhua, Eisenberg Carol A, Eisenberg Leonard M, Gourdie Robert G
Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Dev Dyn. 2003 Aug;227(4):536-43. doi: 10.1002/dvdy.10333.
The heart beat is coordinated by a precisely timed sequence of action potentials propagated through cells of the conduction system. Previously, we have shown that conduction cells in the chick embryo are derived from multipotent, cardiomyogenic progenitors present in the looped, tubular heart. Moreover, analyses of heterogeneity within myocyte clones and cell birth dating have indicated that elaboration of the conduction system occurs by ongoing, localized recruitment from within this multipotent pool. In this study, we have focused on a potential role for Wnt signaling in development of the cardiac conduction system. Treatment of embryonic myocytes from chick with endothelin-1 (ET-1) has been shown to promote expression of markers of Purkinje fiber cells. By using this in vitro model, we find that Wnt11 are Wnt7a are up-regulated in association with ET-1 treatment. Moreover, in situ hybridization reveals expression, although not temporal coincidence of, Wnt11 and Wnt7a in specialized tissues in the developing heart in vivo. Specifically, whereas Wnt11 shows transient and prominent expression in central elements of the developing conduction system (e.g., the His bundle), relative increases in Wnt7a expression emerge at sites consistent with the location of peripheral conduction cells (e.g., subendocardial Purkinje fibers). The patterns of Wnt11 and Wnt7a expression observed in vitro and in the embryonic chick heart appear to be consistent with roles for these two Wnts in differentiation of cardiac conduction tissues.
心跳由通过传导系统细胞传播的精确计时的动作电位序列协调。此前，我们已经表明，鸡胚中的传导细胞源自存在于环状管状心脏中的多能心肌祖细胞。此外，对心肌细胞克隆内的异质性分析和细胞出生时间测定表明，传导系统的形成是通过从这个多能池中持续进行局部募集来实现的。在本研究中，我们聚焦于Wnt信号在心脏传导系统发育中的潜在作用。已证明用内皮素-1（ET-1）处理鸡的胚胎心肌细胞可促进浦肯野纤维细胞标志物的表达。通过使用这个体外模型，我们发现Wnt11和Wnt7a与ET-1处理相关上调。此外，原位杂交揭示了Wnt11和Wnt7a在体内发育中心脏的特殊组织中的表达，尽管不是时间上的巧合。具体而言，虽然Wnt11在发育中的传导系统的中心元件（例如希氏束）中显示出短暂且显著的表达，但Wnt7a表达的相对增加出现在与外周传导细胞位置一致的部位（例如心内膜下浦肯野纤维）。在体外和鸡胚心脏中观察到的Wnt11和Wnt7a表达模式似乎与这两种Wnt在心脏传导组织分化中的作用一致。
