Dachsousl-Fat4 Signaling Controls Endothelial Cell Polarization During Lymphatic Valve Morphogenesis-Brief Report

作者：Pujol Francoise; Hodgson Tina; Martinez Corral Ines; Prats Anne Catherine; Devenport Danelle; Takeichi Masatoshi; Genot Elisabeth; Makinen Taija; Francis West Philippa; Garmy Susini Barbara; Tatin Florence^*

来源：Arteriosclerosis, Thrombosis, and Vascular Biology, 2017, 37(9): 1732-+.

DOI：10.1161/ATVBAHA.117.309818

• cell polarity
• endothelial cells
• intercellular junctions
• lymphangiogenesis
• lymphedema

Objective-The purpose of this study was to investigate the role of Fat4 and Dachsous 1 signaling in the lymphatic vasculature.
Approach and Results-Phenotypic analysis of the lymphatic vasculature was performed in mice lacking functional Fat4 or Dachsousl. The overall architecture of lymphatic vasculature is unaltered, yet both genes are specifically required for lymphatic valve morphogenesis. Valve endothelial cells (Proxl(high) [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 Dachsousl to membrane protrusions and cellular junctions of valve endothelial cells in vivo and in vitro.
Conclusions-Our data demonstrate that Fat4 and Dachsousl are critical regulators of valve morphogenesis. This study highlights that valve defects may contribute to lymphedema in Hennekam syndrome caused by Fat4 mutations.

• 出版日期2017-9
• 单位RIKEN