Dual role for neural crest cells during outflow tract septation in the neural crest-deficient mutant Splotch2H
Dual role for neural crest cells during outflow tract septation in the neural crest-deficient mutant Splotch2H
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DOI：
10.1111/j.1469-7580.2008.01028.x
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发表时间：
2009-02-01
影响因子：
2.4
通讯作者：
Henderson, Deborah J.
中科院分区：
文献类型：
--
作者：
Bradshaw, Lucy;Chaudhry, Bill;Henderson, Deborah J.
Spotch（2 H）（Sp（2 H））是一种公认的神经嵴细胞（NCC）缺陷小鼠模型，其产生一系列心脏流出道畸形，包括总动脉干、右心室双出口、室间隔缺损和咽弓动脉图案缺损，以及其他神经嵴衍生器官系统的缺损。这些缺陷被归因于咽部和流出区域的NCC减少。在这里，我们提供了一个详细的地图NCC内的咽弓和流出道的Sp（2 H）/Sp（2 H）胚胎和胎儿，这与发展的异常解剖结构的这些结构。在大多数Sp（2 H）/Sp（2 H）胚胎中，我们发现咽部区域NCC的缺乏导致咽后弓动脉的稳定失败和早期丢失。此外，主动脉囊背壁中的NCC衍生间充质的显著减少破坏了与远端流出道垫的融合，阻止了流出道分隔的开始并导致共同动脉干。在约25%的Sp（2 H）/Sp（2 H）胚胎中，后弓动脉稳定，主动脉囊背壁和流出垫之间发生融合，开始流出道分隔;这些胚胎发育双出口右心室。因此，在咽部区域需要NCC来稳定后弓动脉和开始流出道分隔。NCC的缺失也破坏了第二心脏区域细胞在咽部和流出区域中的分布。NCC缺陷的这些继发性影响可能导致整体流出表型，表明这两种细胞类型之间的相互作用被破坏可能是许多常见流出缺陷的基础。
Splotch(2H) (Sp(2H)) is a well-recognized mouse model of neural crest cell (NCC) deficiency that develops a spectrum of cardiac outflow tract malformations including common arterial trunk, double outlet right ventricle, ventricular septal defects and pharyngeal arch artery patterning defects, as well as defects in other neural-crest derived organ systems. These defects have been ascribed to reduced NCC in the pharyngeal and outflow regions. Here we provide a detailed map of NCC within the pharyngeal arches and outflow tract of Sp(2H)/Sp(2H) embryos and fetuses, relating this to the development of the abnormal anatomy of these structures. In the majority of Sp(2H)/Sp(2H) embryos we show that deficiency of NCC in the pharyngeal region results in a failure to stabilize, and early loss of, posterior pharyngeal arch arteries. Furthermore, marked reduction in the NCC-derived mesenchyme in the dorsal wall of the aortic sac disrupts fusion with the distal outflow tract cushions, preventing the initiation of outflow tract septation and resulting in common arterial trunk. In around 25% of Sp(2H)/Sp(2H) embryos, posterior arch arteries are stabilized and fusion occurs between the dorsal wall of the aortic sac and the outflow cushions, initiating outflow tract septation; these embryos develop double outlet right ventricle. Thus, NCC are required in the pharyngeal region both for stabilization of posterior arch arteries and initiation of outflow tract septation. Loss of NCC also disrupts the distribution of second heart field cells in the pharyngeal and outflow regions. These secondary effects of NCC deficiency likely contribute to the overall outflow phenotype, suggesting that disrupted interactions between these two cell types may underlie many common outflow defects.