Dachsous1-Fat4信号通路在淋巴管瓣膜形态发生过程中控制内皮细胞极化——简要报告
Dachsous1-Fat4 Signaling Controls Endothelial Cell Polarization During Lymphatic Valve Morphogenesis-Brief Report.
作者信息
Pujol Francoise, Hodgson Tina, Martinez-Corral Ines, Prats Anne-Catherine, Devenport Danelle, Takeichi Masatoshi, Genot Elisabeth, Mäkinen Taija, Francis-West Philippa, Garmy-Susini Barbara, Tatin Florence
机构信息
From the I2MC INSERM UMR 1048, Toulouse Cedex, France (F.P., A.-C.P., B.G.-S., F.T.); Department Craniofacial Development and Stem Cell Biology, King's College London, United Kingdom (T.H., P.F.-W.); Rudbeck Laboratory, Department Immunology, Genetics and Pathology, Uppsala University, Sweden (I.M.-C., T.M.); Department of Molecular Biology, Princeton University, NJ (D.D.); Laboratory for Cell Adhesion and Tissue Patterning, RIKEN Center for Developmental Biology, Kobe, Japan (M.T.); and INSERM, Université de Bordeaux, France (E.G.).
出版信息
Arterioscler Thromb Vasc Biol. 2017 Sep;37(9):1732-1735. doi: 10.1161/ATVBAHA.117.309818. Epub 2017 Jul 13.
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 or . The overall architecture of lymphatic vasculature is unaltered, yet both genes are specifically required for lymphatic valve morphogenesis. Valve endothelial cells (Prox1 [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.
目的
本研究旨在探讨Fat4和Dachsous1信号在淋巴管系统中的作用。
方法与结果
在缺乏功能性 或 的小鼠中对淋巴管系统进行表型分析。淋巴管系统的整体结构未改变，但这两个基因对于淋巴瓣膜形态发生均为特异性必需。瓣膜内皮细胞（Prox1[prospero同源框蛋白1]细胞）方向紊乱，无法形成正常的瓣膜小叶。利用Lifeact-GFP（绿色荧光蛋白）小鼠，我们发现瓣膜内皮细胞显示出显著的肌动蛋白聚合。最后，我们在体内和体外均显示了Dachsous1向瓣膜内皮细胞膜突起和细胞连接的极化募集。
结论
我们的数据表明，Fat4和Dachsous1是瓣膜形态发生的关键调节因子。本研究强调瓣膜缺陷可能导致由Fat4突变引起的亨内坎综合征中的淋巴水肿。
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