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

Abstract

Highlights d PCP components are restricted to apical junctions during pancreas development d The core PCP protein VANGL is planar polarized along the duct d Ectopic basolateral expansion of VANGL cell autonomously downregulates DVL and ROCK d Decreased ROCK activity leads to cell egression, apoptosis, and pancreatic hypoplasia

Single-Cell Trajectory Inference Guided Enhancement of Thyroid Maturation In Vitro Using TGF-Beta Inhibition

“…In addition to the study of TGF-beta and BMP pathway, our trajectory analysis suggests the enrichment of Wnt/PCP signaling components, both ligands and receptors, specifically in mature thyrocytes (Supplementary Figure 4). Given the role of Wnt/PCP in the differentiation and function of endocrine cells in the pancreas (41)(42)(43), our data warrants a detailed analysis of Wnt/PCP pathway in the polarized thyroid follicular cells.…”

Single-cell trajectory inference guided enhancement of thyroid maturationin vitrousing TGF-beta inhibition

“…Notably, Wnt/PCP pathway plays a critical role in the differentiation and function of endocrine cells in the pancreas. Particularly, the pancreatic progenitors, which generate insulin-secreting pancreatic beta-cells, rely on PCP cues for establishing apico-basal polarity that is required for differentiation to endocrine lineage (37,38). Work from the group of Grapin-Botton has demonstrated the requirement for Celsr2 and Celsr3 in pancreas morphogenesis (37).…”

Pancreas morphogenesis: Branching in and then out

“…The cell polarity is now firmly established as classical markers of apical polarity such as PAR3/6, Crumbs3, and aPKC are detected along the apical surface of the lumen-lining cells, while Collagen IV and Laminin mark their basal side (Kesavan et al, 2009;Villasenor et al, 2010). Concomitant to this acquisition of polarity along the apico-basal axis, the planar polarity components VANGL1/2 and Frizzled3 are detected around the apical junctions (Flasse et al, 2020). Our understanding of the lumen expansion process in the pancreas is rudimentary.…”

“…Actomyosin contractility plays an important role in driving the changes in organ shape associated with branching in several organs (Wang et al, 2017). The phosphorylated form of myosin regulatory light chain (pMLC), a substrate of Rho-associated kinase (ROCK) and effector/read-out of actomyosin-based contraction, is polarized at apical cell junctions of all epithelial cells in a pattern similar to the actin network (Bankaitis, Bechard, Gu, Magnuson, & Wright, 2018;Flasse et al, 2020). Although this expression pattern in suggestive of a role of the ROCK pathway and the downstream actomyosin contractility in pancreas remodeling, E11.5 explants treated with a ROCK inhibitor do not show major defects in lumen morphology or branching (Azizoglu et al, 2017).…”