Developmental Origin, Growth, and Three-Dimensional Architecture of the Atrioventricular Conduction Axis of the Mouse Heart
Developmental Origin, Growth, and Three-Dimensional Architecture of the Atrioventricular Conduction Axis of the Mouse Heart
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DOI：
10.1161/circresaha.110.222992
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发表时间：
2010-09-17
影响因子：
20.1
通讯作者：
Christoffels, Vincent M.
中科院分区：
文献类型：
--
作者：
Aanhaanen, Wim T. J.;Mommersteeg, Mathilda T. M.;Christoffels, Vincent M.
理由：临床上重要的房室传导轴结构复杂且异质，其分子组成和发育起源尚不确定。目的：评估出生后小鼠心脏中房室传导轴的分子组成和 3D 结构，并确定其组成部分的发育起源。方法和结果：我们生成了房室传导轴的交互式 3D 模型。 使用 Tbx3、Hcn4、Cx40、Cx43、Cx45 和 Nav1.5 的表达模式对小鼠心脏的房室连接区进行分析，这些对传导系统功能很重要。我们在二尖瓣和三尖瓣交界处以及房间隔底部发现了广泛的八字形结节和移行细胞环。这些环包括紧凑节点和节点扩展。然后，我们使用遗传谱系标记工具（Tbx2（+ Cre）、Mef2c-AHF-Cre、Tbx18（+/Cre））以及形态测量分析来评估轴特定组件的发育起源。大多数心房部件，包括房室环和致密结，均源自胚胎房室管。相反，房室束（包括房室结的下部细胞）源自心室心肌。静脉窦、心外膜或背侧间质突起对心肌传导系统没有贡献。结论：房室传导轴包含多个具有独特分子特征的域。心房部分从胚胎房室管增殖，连同来自发育中的房间隔的肌细胞一起增殖。房室束和下结细胞来源于心室心肌。 （Circ Res. 2010；107:728-736。）
Rationale: The clinically important atrioventricular conduction axis is structurally complex and heterogeneous, and its molecular composition and developmental origin are uncertain.Objective: To assess the molecular composition and 3D architecture of the atrioventricular conduction axis in the postnatal mouse heart and to define the developmental origin of its component parts.Methods and Results: We generated an interactive 3D model of the atrioventricular junctions in the mouse heart using the patterns of expression of Tbx3, Hcn4, Cx40, Cx43, Cx45, and Nav1.5, which are important for conduction system function. We found extensive figure-of-eight rings of nodal and transitional cells around the mitral and tricuspid junctions and in the base of the atrial septum. The rings included the compact node and nodal extensions. We then used genetic lineage labeling tools (Tbx2(+Cre), Mef2c-AHF-Cre, Tbx18(+/Cre)), along with morphometric analyses, to assess the developmental origin of the specific components of the axis. The majority of the atrial components, including the atrioventricular rings and compact node, are derived from the embryonic atrioventricular canal. The atrioventricular bundle, including the lower cells of the atrioventricular node, in contrast, is derived from the ventricular myocardium. No contributions to the conduction system myocardium were identified from the sinus venosus, the epicardium, or the dorsal mesenchymal protrusion.Conclusions: The atrioventricular conduction axis comprises multiple domains with distinctive molecular signatures. The atrial part proliferates from the embryonic atrioventricular canal, along with myocytes derived from the developing atrial septum. The atrioventricular bundle and lower nodal cells are derived from ventricular myocardium. (Circ Res. 2010;107:728-736.)