Neural crest cells retain multipotential characteristics in the developing valves and label the cardiac conduction system
Neural crest cells retain multipotential characteristics in the developing valves and label the cardiac conduction system
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DOI：
10.1161/01.res.0000227505.19472.69
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发表时间：
2006-06-23
影响因子：
20.1
通讯作者：
Robbins, Jeffrey
中科院分区：
文献类型：
--
作者：
Nakamura, Tomoki;Colbert, Melissa C.;Robbins, Jeffrey
多能神经嵴细胞（NCCs）是心血管发育的主要心外成分。尽管在早期发育阶段被认为是动脉瓣膜的贡献细胞，但NCC在后期或成年心脏瓣膜中的持续性是有争议的。我们分析了NCC的持久性和贡献的半月瓣和房室（AV）瓣膜在成熟的心脏。驱动Cre重组酶的两个NCC特异性启动子Wnt 1-Cre和P0-Cre与floxed报告小鼠R26 R或CAG-CAT-EGFP交配，以绘制NCC命运。在成年期进行心房间隔（AP）分离前对心脏进行分析。如前所述，在AP分隔前，在腹侧和背侧流出垫中检测到强烈的NCC标记。与以前的报道相反，我们发现大量的标记细胞持续存在于晚期胎儿，新生儿和成人心脏的半月瓣中。此外，在AV瓣膜中也发现了NCC，几乎仅在隔叶中。房室瓣中的NCC表达黑素细胞和神经源性标记物。然而，在近端心脏传导系统标记的细胞表现出神经原性和胶质原性标记，而一些NCC表达没有分化特异性标记。这些结果表明，心脏NCC有助于成熟的瓣膜和心脏传导系统，并在发育后期保留多能特性。
Multipotent neural crest cells (NCCs) are a major extracardiac component of cardiovascular development. Although recognized as contributing cells to the arterial valves at early developmental stages, NCC persistence in the valves at later times or in the adult heart is controversial. We analyzed NCC persistence and contributions to both semilunar and atrioventricular ( AV) valves in the mature heart. Two NCC-specific promoters driving Cre recombinase, Wnt1-Cre and P0-Cre, were mated with floxed reporter mice, R26R or CAG-CAT-EGFP, to map NCC fate. Hearts were analyzed before aorticopulmonary (AP) septation through adult stages. As previously demonstrated, strong NCC labeling was detected in ventral and dorsal outflow cushions before AP septation. In contrast to previous reports, we found that substantial numbers of labeled cells persisted in the semilunar valves in late fetal, neonatal, and adult hearts. Furthermore, NCCs were also found in the AV valves, almost exclusively in the septal leaflets. NCCs in the AV valves expressed melanocytic and neurogenic markers. However, cells labeled in the proximal cardiac conduction system exhibited neurogenic and gliagenic markers, whereas some NCCs expressed no differentiation specific markers. These results suggest that cardiac NCCs contribute to the mature valves and the cardiac conduction system and retain multipotent characteristics late in development.