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

다국어 초록 (Multilingual 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.










The vascular endothelial cadherin, VE‐cadherin, mediates endothelial adhesion and is indispensible for blood vessel development and permeability regulation. This study uses conditional mouse models to demonstrate a tissue‐specific role for VE‐Cadherin in lymph vessel bed development and maintenance.



Deletion of VE‐cadherin in fetal lymphatic endothelial cells in mice results in edema and prenatal lethality.

Adult dermal lymph vessels are largely unaffected by loss of VE‐cadherin due to an increased expression of junction molecules.

Mesenteric lymphatic collectors deteriorate and form endothelial cell sheets upon loss of VE‐cadherin.

A lymphangiogenic environment and increased YAP/TAZ signaling support mesenteric LEC hyperplasia in VE‐cadherin‐depleted mice.

Intestinal villi fragment or bloat after mesenteric lymph collector death.


Conditional deletion of vascular endothelial (VE)‐cadherin in mouse reveals a tissue‐specific role in lymph vessel bed development and maintenance, thus adding to the known requirement for VE‐cadherin in blood vessel formation.