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.
The Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
Cell Rep. 2020 May 26;31(8):107677. doi: 10.1016/j.celrep.2020.107677.
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.
细胞极性对于许多上皮组织的结构和功能至关重要。在这里，我们表明，平面细胞极性（PCP）成分的顶端限制对于维持上皮完整性是必要的。我们使用哺乳动物胰腺作为模型，发现核心 PCP 途径的成分，如跨膜蛋白 Van Gogh-like（VANGL），在几天的时间内会被限制在顶端。VANGL 定位扩展到祖细胞的基底外侧膜会导致它们死亡并破坏上皮完整性。VANGL 基底外侧扩展不会影响顶底极性，但通过减少 Dishevelled 及其下游靶标 ROCK 来作用于 Vangl 被错误定位的细胞。ROCK 活性的这种降低导致祖细胞迁出、死亡，最终导致胰腺发育不良。因此，VANGL 依赖性 PCP 信号的精确时空调节对于胰腺形态发生至关重要。
