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(Circulation Research. 2008;102:1169.)
© 2008 American Heart Association, Inc.

Reviews

Notch Signaling in Cardiac Development

Kyle Niessen, Aly Karsan

From the Departments of Medical Biophysics (K.N., A.K.) and Pathology and Laboratory Medicine (A.K.), British Columbia Cancer Agency, Vancouver; and the Experimental Medicine Program (K.N., A.K.) and Department of Pathology and Laboratory Medicine (A.K.), University of British Columbia, Vancouver, Canada.

Correspondence to Aly Karsan, Department of Medical Biophysics, British Columbia Cancer Research Centre, 675 W 10th Ave, Vancouver, BC, Canada V5Z 1L3. E-mail akarsan{at}bccrc.ca

This Review is part of a thematic series on Notch in the Cardiovascular System, which includes the following articles: Crosstalk Between Vascular Endothelial Growth Factor, Notch, and Transforming Growth Factor-β in Vascular Morphogenesis

Notch Signaling in Cardiac Development

Notch and Vascular Smooth Muscle Phenotype
Aly Karsan Guest Editor

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.

Key Words: Notch • cardiac development • endothelial–mesenchymal transformation • vasculogenesis • angiogenesis

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