Notch signaling in cardiac development

被引:212
作者
Niessen, Kyle [2 ,3 ]
Karsan, Aly [1 ,2 ,3 ,4 ]
机构
[1] British Columbia Canc Agcy, Dept Pathol & Lab Med, Vancouver, BC, Canada
[2] British Columbia Canc Agcy, Dept Med Biophys, Vancouver, BC, Canada
[3] Univ British Columbia, Expt Med Program, Vancouver, BC V5Z 1M9, Canada
[4] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada
关键词
Notch; cardiac development; endothelial-mesenchymal transformation; vasculogenesis; angiogenesis;
D O I
10.1161/CIRCRESAHA.108.174318
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The Notch signaling pathway has been demonstrated to play a critical role during mammalian cardiac development based on recent findings from gene-targeted mice. In addition, mutations in the Notch signaling pathway have been associated with human congenital heart defects such as Alagille syndrome, bicuspid aortic valve disease, calcification of the heart valves, and ventricular septal defects. Recently, it was demonstrated that Notch activation in the endocardium regulates ventricular myocardial development and that the Notch downstream target genes Hey1 and Hey2 are required for the establishment of the atrioventricular canal myocardial boundary. The Notch pathway has previously been implicated in regulating endothelial-to-mesenchymal transition during development of the heart valves, and recent reports further dissect the role of individual Notch downstream target genes during this process. In addition, a role for the Notch pathway during cardiac neural crest cell development has been identified, which provides a potential mechanism for the findings seen in Alagille syndrome. This review focuses on recently reported findings that elucidate mechanisms regulated by the Notch pathway during ventricular, atrioventricular canal, and outflow tract development.
引用
收藏
页码:1169 / 1181
页数:13
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