Lineage and morphogenetic analysis of the cardiac valves
Lineage and morphogenetic analysis of the cardiac valves
复制标题
DOI：
10.1161/01.res.0000141429.13560.cb
复制
发表时间：
2004-09-17
影响因子：
20.1
通讯作者：
Christoffels, VM
中科院分区：
文献类型：
--
作者：
de Lange, FJ;Moorman, AFM;Christoffels, VM
我们使用遗传谱系标记系统来建立3种特定细胞类型的后代对心脏瓣膜的物质贡献。因此，我们在发育过程中不可逆地标记了心肌细胞（α MHC-Cre+）、内皮细胞（Tie 2-Cre+）和神经嵴细胞（Wnt 1-Cre+），并评估了它们对最终瓣膜复合体的最终贡献。发现二尖瓣和三尖瓣的小叶和腱索、房室纤维连续性以及流出道瓣膜的小叶均由源自内膜的间充质生成，心肌和神经嵴谱系细胞无实质性贡献。鸡鹌鹑嵌合体的分析显示，没有任何实质性的贡献，从proepicardially衍生的细胞。分子和形态发生学分析揭示了房室瓣形成的几个新方面。在二尖瓣和三尖瓣的壁叶形成过程中可以看到明显的相似性。这些瓣叶是通过房室心肌片突出和生长到心室腔中形成的，随后在其表面上形成瓣膜间充质，而不是通过侧垫从心室心肌壁分层形成的。随后通过细胞凋亡过程去除心肌层。相反，二尖瓣的主动脉瓣叶、三尖瓣的隔叶以及这些瓣膜之间的房室纤维连续性从下房室垫和上级房室垫的间充质发育而来。在发育后期，三尖瓣隔叶与肌性室间隔分离。
We used a genetic lineage-labeling system to establish the material contributions of the progeny of 3 specific cell types to the cardiac valves. Thus, we labeled irreversibly the myocardial (alphaMHC-Cre+), endocardial (Tie2-Cre+), and neural crest (Wnt1-Cre+) cells during development and assessed their eventual contribution to the definitive valvar complexes. The leaflets and tendinous cords of the mitral and tricuspid valves, the atrioventricular fibrous continuity, and the leaflets of the outflow tract valves were all found to be generated from mesenchyme derived from the endocardium, with no substantial contribution from cells of the myocardial and neural crest lineages. Analysis of chicken-quail chimeras revealed absence of any substantial contribution from proepicardially derived cells. Molecular and morphogenetic analysis revealed several new aspects of atrioventricular valvar formation. Marked similarities are seen during the formation of the mural leaflets of the mitral and tricuspid valves. These leaflets form by protrusion and growth of a sheet of atrioventricular myocardium into the ventricular lumen, with subsequent formation of valvar mesenchyme on its surface rather than by delamination of lateral cushions from the ventricular myocardial wall. The myocardial layer is subsequently removed by the process of apoptosis. In contrast, the aortic leaflet of the mitral valve, the septal leaflet of the tricuspid valve, and the atrioventricular fibrous continuity between these valves develop from the mesenchyme of the inferior and superior atrioventricular cushions. The tricuspid septal leaflet then delaminates from the muscular ventricular septum late in development.