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Distinct roles of VE ‐cadherin for development and maintenance of specific lymph vessel beds
Author(s) -
Hägerling René,
Hoppe Esther,
Dierkes Cathrin,
Stehling Martin,
Makinen Taija,
Butz Stefan,
Vestweber Dietmar,
Kiefer Friedemann
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201798271
Subject(s) - lymphatic system , biology , ve cadherin , lymphatic endothelium , downregulation and upregulation , lymphatic vessel , cadherin , microbiology and biotechnology , lymphangiogenesis , mesenteric lymph nodes , lymph , endothelium , blood vessel , pathology , anatomy , immunology , cell , endocrinology , medicine , immune system , genetics , biochemistry , cancer , gene , metastasis
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.