Planar Cell Polarity Protein Celsr1 Regulates Endothelial Adherens Junctions and Directed Cell Rearrangements during Valve Morphogenesis

• Published in: Developmental cell Vol. 26; no. 1; pp. 31 - 44
• Main Authors: Tatin, Florence, Taddei, Andrea, Weston, Anne, Fuchs, Elaine, Devenport, Danelle, Tissir, Fadel, Makinen, Taija
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.07.2013; Cell Press
• Subjects: abnormal development; adherens junctions; Adherens Junctions - metabolism; Animals; Antigens, CD - genetics; Antigens, CD - metabolism; Cadherins - genetics; Cadherins - metabolism; Cell Communication; Cell Line; Cell Movement; Cell Polarity; Embryo, Mammalian - embryology; Embryo, Mammalian - metabolism; endothelial cells; Endothelial Cells - cytology; Endothelial Cells - metabolism; Female; Fibronectins - genetics; Fibronectins - metabolism; Humans; Lymphatic Vessels - metabolism; Mice; Mice, Inbred C57BL; Morphogenesis; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; proteins; pseudopodia; Pseudopodia - metabolism; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Signal Transduction
• ISSN: 1534-5807; 1878-1551; 1878-1551
• DOI: 10.1016/j.devcel.2013.05.015

Planar cell polarity (PCP) signaling controls tissue morphogenesis by coordinating collective cell behaviors. We show a critical role for the core PCP proteins Celsr1 and Vangl2 in the complex morphogenetic process of intraluminal valve formation in lymphatic vessels. We found that valve-forming endothelial cells undergo elongation, reorientation, and collective migration into the vessel lumen as they initiate valve leaflet formation. During this process, Celsr1 and Vangl2 are recruited from endothelial filopodia to discrete membrane domains at cell-cell contacts. Celsr1- or Vangl2-deficient mice show valve aplasia due to failure of endothelial cells to undergo rearrangements and adopt perpendicular orientation at valve initiation sites. Mechanistically, we show that Celsr1 regulates dynamic cell movements by inhibiting stabilization of VE-cadherin and maturation of adherens junctions. These findings reveal a role for PCP signaling in regulating adherens junctions and directed cell rearrangements during vascular development. [Display omitted] •Endothelial cells undergo collective migration during lymphatic valve morphogenesis•PCP signaling directs rearrangements of valve-forming endothelial cells•PCP components localize to filopodia and cell-cell contacts in valve endothelia•PCP signaling regulates adherens junction formation and stabilization Tatin et al. show that endothelial cells undergo elongation, reorientation, and collective migration into the vessel lumen as they initiate valve leaflet formation during lymphatic morphogenesis. The planar cell polarity proteins Celsr1 and Vangl2 regulate dynamic rearrangements of valve-forming cells by inhibiting stabilization of VE-cadherin and maturation of adherens junctions.