title: Planar cell polarity protein Celsr1 regulates endothelial adherens junctions and directed cell rearrangements during valve morphogenesis.
abstract: 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.
authors.affiliation: Lymphatic Development Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Florence
authors.initials: F
authors.lastname: Tatin
authors.forename: Andrea
authors.initials: A
authors.lastname: Taddei
authors.forename: Anne
authors.initials: A
authors.lastname: Weston
authors.forename: Elaine
authors.initials: E
authors.lastname: Fuchs
authors.forename: Danelle
authors.initials: D
authors.lastname: Devenport
authors.forename: Fadel
authors.initials: F
authors.lastname: Tissir
authors.forename: Taija
authors.initials: T
authors.lastname: Makinen
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002450:Cell Communication; D002460:Cell Line; D002465:Cell Movement; D016764:Cell Polarity; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D042601:Lymphatic Vessels / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009024:Morphogenesis; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D005353:Fibronectins; D009419:Nerve Tissue Proteins; D043562:Receptors, G-Protein-Coupled; D000099152:Cadherin 5; C117380:Celsr1 protein, mouse; C431577:Ltap protein, mouse; C572454:extra domain A fibronectin, mouse