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

被引：28

作者：

Pujol, Francoise ^{[1
]}

Hodgson, Tina ^{[2
]}

Martinez-Corral, Ines ^{[3
]}

Prats, Anne-Catherine ^{[1
]}

Devenport, Danelle ^{[4
]}

Takeichi, Masatoshi ^{[5
]}

Genot, Elisabeth ^{[6
]}

Makinen, Taija ^{[3
]}

Francis-West, Philippa ^{[2
]}

Garmy-Susini, Barbara ^{[1
]}

Tatin, Florence ^{[1
]}

机构：

[1] I2MC INSERM UMR 1048, Toulouse, France

[2] Kings Coll London, Dept Craniofacial Dev & Stem Cell Biol, London, England

[3] Uppsala Univ, Dept Immunol Genet & Pathol, Rudbeck Lab, Uppsala, Sweden

[4] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA

[5] RIKEN Ctr Dev Biol, Lab Cell Adhes & Tissue Patterning, Kobe, Hyogo, Japan

[6] Univ Bordeaux, INSERM, Bordeaux, France

来源：

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY | 2017年 / 37卷 / 09期

基金：

英国生物技术与生命科学研究理事会; 瑞典研究理事会;

关键词：

cell polarity; endothelial cells; intercellular junctions; lymphangiogenesis; lymphedema; VAN MALDERGEM SYNDROME; NEURONAL MIGRATION; POLARITY; MUTATIONS; DCHS1; JUNCTIONS;

D O I：

10.1161/ATVBAHA.117.309818

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：1732 / +

页数：14

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