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

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1732-1735
Number of pages4
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Issue number9
Early online date13 Jul 2017
Publication statusPublished - 1 Sept 2017


  • cell polarity
  • endothelial cells
  • intercellular junctions
  • lymphangiogenesis
  • lymphedema


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