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Publication : Apical Restriction of the Planar Cell Polarity Component VANGL in Pancreatic Ducts Is Required to Maintain Epithelial Integrity.

First Author  Flasse L Year  2020
Journal  Cell Rep Volume  31
Issue  8 Pages  107677
PubMed ID  32460029 Mgi Jnum  J:306166
Mgi Id  MGI:6714724 Doi  10.1016/j.celrep.2020.107677
Citation  Flasse L, et al. (2020) Apical Restriction of the Planar Cell Polarity Component VANGL in Pancreatic Ducts Is Required to Maintain Epithelial Integrity. Cell Rep 31(8):107677
abstractText  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.
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