Apical Restriction of the Planar Cell Polarity Component VANGL in Pancreatic Ducts Is Required to Maintain Epithelial Integrity
Lydie Flasse,
Siham Yennek,
Cédric Cortijo,
Irene Seijo Barandiaran,
Marine R.-C. Kraus,
Anne Grapin-Botton
Affiliations
Lydie Flasse
The Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany; Corresponding author
Siham Yennek
The Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
Cédric Cortijo
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausannne, Switzerland
Irene Seijo Barandiaran
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
Marine R.-C. Kraus
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausannne, Switzerland
Anne Grapin-Botton
The Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany; Corresponding author
Summary: Cell polarity is essential for the architecture and function of numerous epithelial tissues. Here, we show that apical restriction of planar cell polarity (PCP) components is necessary for the maintenance of epithelial integrity. Using the mammalian pancreas as a model, we find that components of the core PCP pathway, such as the transmembrane protein Van Gogh-like (VANGL), become apically restricted over a period of several days. Expansion of VANGL localization to the basolateral membranes of progenitors leads to their death and disruption of the epithelial integrity. VANGL basolateral expansion does not affect apico-basal polarity but acts in the cells where Vangl is mislocalized by reducing Dishevelled and its downstream target ROCK. This reduction in ROCK activity culminates in progenitor cell egression, death, and eventually pancreatic hypoplasia. Thus, precise spatiotemporal modulation of VANGL-dependent PCP signaling is crucial for proper pancreatic morphogenesis.
