Dachsous1–Fat4 signaling controls endothelial cell polarization during lymphatic valve morphogenesis—brief report
F Pujol, T Hodgson, I Martinez-Corral… - … , and vascular biology, 2017 - Am Heart Assoc
F Pujol, T Hodgson, I Martinez-Corral, AC Prats, D Devenport, M Takeichi, E Genot…
Arteriosclerosis, thrombosis, and vascular biology, 2017•Am Heart AssocObjective—The purpose of this study was to investigate the role of Fat4 and Dachsous1
signaling in the lymphatic vasculature. Approach and Results—Phenotypic analysis of the
lymphatic vasculature was performed in mice lacking functional Fat4 or Dachsous1. The
overall architecture of lymphatic vasculature is unaltered, yet both genes are specifically
required for lymphatic valve morphogenesis. Valve endothelial cells (Prox1high [prospero
homeobox protein 1] cells) are disoriented and failed to form proper valve leaflets. Using …
signaling in the lymphatic vasculature. Approach and Results—Phenotypic analysis of the
lymphatic vasculature was performed in mice lacking functional Fat4 or Dachsous1. The
overall architecture of lymphatic vasculature is unaltered, yet both genes are specifically
required for lymphatic valve morphogenesis. Valve endothelial cells (Prox1high [prospero
homeobox protein 1] cells) are disoriented and failed to form proper valve leaflets. Using …
Objective
The purpose of this study was to investigate the role of Fat4 and Dachsous1 signaling in the lymphatic vasculature.
Approach and Results
Phenotypic analysis of the lymphatic vasculature was performed in mice lacking functional Fat4 or Dachsous1. The overall architecture of lymphatic vasculature is unaltered, yet both genes are specifically required for lymphatic valve morphogenesis. Valve endothelial cells (Prox1high [prospero homeobox protein 1] cells) are disoriented and failed to form proper valve leaflets. Using Lifeact-GFP (green fluorescent protein) mice, we revealed that valve endothelial cells display prominent actin polymerization. Finally, we showed the polarized recruitment of Dachsous1 to membrane protrusions and cellular junctions of valve endothelial cells in vivo and in vitro.
Conclusions
Our data demonstrate that Fat4 and Dachsous1 are critical regulators of valve morphogenesis. This study highlights that valve defects may contribute to lymphedema in Hennekam syndrome caused by Fat4 mutations.
Am Heart Assoc