Arteriosclerosis, thrombosis, and vascular biology · 2017
Dachsous1-Fat4 Signaling Controls Endothelial Cell Polarization During Lymphatic Valve Morphogenesis-Brief Report.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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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
Аннотация
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.
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.
Предметные рубрики MeSH
Actin CytoskeletonActinsAnimalsCadherinsCell MovementCells, CulturedCraniofacial AbnormalitiesEndothelial CellsEndothelium, LymphaticFluorescent Antibody TechniqueGenetic Predisposition to DiseaseGreen Fluorescent ProteinsHomeodomain ProteinsHumansLymphangiectasis, IntestinalLymphangiogenesisLymphatic VesselsLymphedemaMice, KnockoutMutationPhenotypeProtein MultimerizationSignal TransductionTransfectionTumor Suppressor ProteinsProspero-Related Homeobox 1 Protein