1. Distinct roles of VE-cadherin for development and maintenance of specific lymph vessel beds
- Author
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Haegerling, Rene, Hoppe, Esther, Dierkes, Cathrin, Stehling, Martin, Mäkinen, Taija, Butz, Stefan, Vestweber, Dietmar, Kiefer, Friedemann, Haegerling, Rene, Hoppe, Esther, Dierkes, Cathrin, Stehling, Martin, Mäkinen, Taija, Butz, Stefan, Vestweber, Dietmar, and Kiefer, Friedemann
- Abstract
Endothelial cells line blood and lymphatic vessels and form intercellular junctions, which preserve vessel structure and integrity. The vascular endothelial cadherin, VE-cadherin, mediates endothelial adhesion and is indispensible for blood vessel development and permeability regulation. However, its requirement for lymphatic vessels has not been addressed. During development, VE-cadherin deletion in lymphatic endothelial cells resulted in abortive lymphangiogenesis, edema, and prenatal death. Unexpectedly, inducible postnatal or adult deletion elicited vessel bed-specific responses. Mature dermal lymph vessels resisted VE-cadherin loss and maintained button junctions, which was associated with an upregulation of junctional molecules. Very different, mesenteric lymphatic collectors deteriorated and formed a strongly hyperplastic layer of lymphatic endothelial cells on the mesothelium. This massive hyperproliferation may have been favored by high mesenteric VEGF-C expression and was associated with VEGFR-3 phosphorylation and upregulation of the transcriptional activator TAZ. Finally, intestinal lacteals fragmented into cysts or became highly distended possibly as a consequence of the mesenteric defects. Taken together, we demonstrate here the importance of VE-cadherin for lymphatic vessel development and maintenance, which is however remarkably vessel bed-specific.
- Published
- 2018
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