Planar cell polarity protein Celsr1 regulates endothelial adherens junctionsand directed cell rearrangements during lymphatic valve morphogenesis.
(2013) Developmental Cell — Vol. 26, n° 1, p. 31-44 (2013)
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- Authors
Tissir, Fadel 
- Abstract
- Planar cell polarity (PCP) signaling controls tissue morphogenesis by coordinating collective cell behaviours. Here 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 show 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 novel role for PCP signaling in regulating adherens junctions and directed cell rearrangements during vascular development.
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Citations
Tatin, F., Taddei, A., Weston, A., Fuchs, E., Davenport, D., Tissir, F., & Makinen, T. (2013). Planar cell polarity protein Celsr1 regulates endothelial adherens junctionsand directed cell rearrangements during lymphatic valve morphogenesis. Developmental Cell, 26(1), 31-44. https://doi.org/10.1016/j.devcel.2013.05.015 (Original work published 2013)