Dachsous1-Fat4 Signaling Controls Endothelial Cell Polarization during Lymphatic Valve Morphogenesis - Brief Report

Francoise Pujol; Tina Hodgson; Ines Martinez-Corral; Anne Catherine Prats; Danelle Devenport; Masatoshi Takeichi; Elisabeth Genot; Taija Mäkinen; Philippa Francis-West; Barbara Garmy-Susini; Florence Tatin

doi:10.1161/ATVBAHA.117.309818

Dachsous1-Fat4 Signaling Controls Endothelial Cell Polarization during Lymphatic Valve Morphogenesis - Brief Report

Francoise Pujol, Tina Hodgson, Ines Martinez-Corral, Anne Catherine Prats, Danelle Devenport, Masatoshi Takeichi, Elisabeth Genot, Taija Mäkinen, Philippa Francis-West, Barbara Garmy-Susini, Florence Tatin^*

^*Corresponding author for this work

Centre for Craniofacial & Regenerative Biology

Research output: Contribution to journal › Article › peer-review

31 Citations (Scopus)

Abstract

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 (Prox1^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 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.

Original language	English
Pages (from-to)	1732-1735
Number of pages	4
Journal	Arteriosclerosis, Thrombosis, and Vascular Biology
Volume	37
Issue number	9
Early online date	13 Jul 2017
DOIs	https://doi.org/10.1161/ATVBAHA.117.309818
Publication status	Published - 1 Sept 2017

Keywords

cell polarity
endothelial cells
intercellular junctions
lymphangiogenesis
lymphedema

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1161/ATVBAHA.117.309818

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Pujol, F., Hodgson, T., Martinez-Corral, I., Prats, A. C., Devenport, D., Takeichi, M., Genot, E., Mäkinen, T., Francis-West, P., Garmy-Susini, B., & Tatin, F. (2017). Dachsous1-Fat4 Signaling Controls Endothelial Cell Polarization during Lymphatic Valve Morphogenesis - Brief Report. Arteriosclerosis, Thrombosis, and Vascular Biology, 37(9), 1732-1735. https://doi.org/10.1161/ATVBAHA.117.309818

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title = "Dachsous1-Fat4 Signaling Controls Endothelial Cell Polarization during Lymphatic Valve Morphogenesis - Brief Report",

abstract = "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.",

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author = "Francoise Pujol and Tina Hodgson and Ines Martinez-Corral and Prats, {Anne Catherine} and Danelle Devenport and Masatoshi Takeichi and Elisabeth Genot and Taija M{\"a}kinen and Philippa Francis-West and Barbara Garmy-Susini and Florence Tatin",

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Pujol, F, Hodgson, T, Martinez-Corral, I, Prats, AC, Devenport, D, Takeichi, M, Genot, E, Mäkinen, T, Francis-West, P, Garmy-Susini, B & Tatin, F 2017, 'Dachsous1-Fat4 Signaling Controls Endothelial Cell Polarization during Lymphatic Valve Morphogenesis - Brief Report', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 37, no. 9, pp. 1732-1735. https://doi.org/10.1161/ATVBAHA.117.309818

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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

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.

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KW - endothelial cells

KW - intercellular junctions

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Dachsous1-Fat4 Signaling Controls Endothelial Cell Polarization during Lymphatic Valve Morphogenesis - Brief Report

Abstract

Keywords

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