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EMBO J. 2018 Nov 15;37(22). pii: e98271. doi: 10.15252/embj.201798271. Epub 2018 Oct 8.

Distinct roles of VE-cadherin for development and maintenance of specific lymph vessel beds.

Author information

1
Mammalian Cell Signaling Laboratory, Max Planck Institute for Molecular Biomedicine, Münster, Germany.
2
European Institute for Molecular Imaging (EIMI), University of Münster, Münster, Germany.
3
Flow Cytometry Unit, Max Planck Institute for Molecular Biomedicine, Münster, Germany.
4
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
5
Department Vascular Cell Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany.
6
DFG Cluster of Excellence 1003 "CiM - Cells in Motion", Münster, Germany.
7
Mammalian Cell Signaling Laboratory, Max Planck Institute for Molecular Biomedicine, Münster, Germany fkiefer@gwdg.de.

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.

KEYWORDS:

VE‐cadherin; YAP/TAZ; lymph vessels; lymphatic valves; vascular heterogeneity

PMID:
30297530
PMCID:
PMC6236332
[Available on 2019-11-15]
DOI:
10.15252/embj.201798271

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