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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Dermis / embryology*
  • Endothelial Cells / metabolism
  • Gene Deletion
  • Gene Expression Regulation, Developmental*
  • Lymphangiogenesis*
  • Lymphatic Vessels / metabolism*
  • Mesentery / embryology*
  • Mice
  • Vascular Endothelial Growth Factor C / genetics
  • Vascular Endothelial Growth Factor C / metabolism
  • Vascular Endothelial Growth Factor Receptor-3 / genetics
  • Vascular Endothelial Growth Factor Receptor-3 / metabolism


  • Antigens, CD
  • Cadherins
  • Vascular Endothelial Growth Factor C
  • cadherin 5
  • vascular endothelial growth factor C, mouse
  • Vascular Endothelial Growth Factor Receptor-3