Endothelial cells express two classic cadherins, VE-cadherin and N-cadherin. The importance of VE-cadherin in vascular development is well known; however, the function of N-cadherin in endothelial cells remains poorly understood. Contrary to previous studies, we found that N-cadherin localizes to endothelial cell–cell junctions in addition to its well-known diffusive membrane expression. To investigate the role of N-cadherin in vascular development, N-cadherin was specifically deleted from endothelial cells in mice. Loss of N-cadherin in endothelial cells results in embryonic lethality at mid-gestation due to severe vascular defects. Intriguingly, loss of N-cadherin caused a significant decrease in VE-cadherin and its cytoplasmic binding partner, p120ctn. The down-regulation of both VE-cadherin and p120ctn was confirmed in cultured endothelial cells using small interfering RNA to knockdown N-cadherin. We also show that N-cadherin is important for endothelial cell proliferation and motility. These findings provide a novel paradigm by which N-cadherin regulates angiogenesis, in part, by controlling VE-cadherin expression at the cell membrane.
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11 April 2005
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April 04 2005
N-cadherin acts upstream of VE-cadherin in controlling vascular morphogenesis
Yang Luo,
Yang Luo
Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
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Glenn L. Radice
Glenn L. Radice
Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
Search for other works by this author on:
Yang Luo
Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
Glenn L. Radice
Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
Correspondence to Glenn Radice: [email protected]
Abbreviations used in this paper: EC, endothelial cell; HMVEC, human dermal microvascular endothelial cells; HUVEC, human umbilical vein endothelial cells; PECAM, platelet endothelial cell adhesion molecule; siRNA, small interfering RNA.
Received:
November 22 2004
Accepted:
February 25 2005
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2005
J Cell Biol (2005) 169 (1): 29–34.
Article history
Received:
November 22 2004
Accepted:
February 25 2005
Citation
Yang Luo, Glenn L. Radice; N-cadherin acts upstream of VE-cadherin in controlling vascular morphogenesis . J Cell Biol 11 April 2005; 169 (1): 29–34. doi: https://doi.org/10.1083/jcb.200411127
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