TY - JOUR
T1 - Dachsous1-Fat4 Signaling Controls Endothelial Cell Polarization during Lymphatic Valve Morphogenesis - Brief Report
AU - Pujol, Francoise
AU - Hodgson, Tina
AU - Martinez-Corral, Ines
AU - Prats, Anne Catherine
AU - Devenport, Danelle
AU - Takeichi, Masatoshi
AU - Genot, Elisabeth
AU - Mäkinen, Taija
AU - Francis-West, Philippa
AU - Garmy-Susini, Barbara
AU - Tatin, Florence
N1 - Publisher Copyright:
© 2017 American Heart Association, Inc.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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.
AB - 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.
KW - cell polarity
KW - endothelial cells
KW - intercellular junctions
KW - lymphangiogenesis
KW - lymphedema
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U2 - 10.1161/ATVBAHA.117.309818
DO - 10.1161/ATVBAHA.117.309818
M3 - Article
C2 - 28705793
AN - SCOPUS:85023746673
SN - 1079-5642
VL - 37
SP - 1732
EP - 1735
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
IS - 9
ER -