The core planar cell polarity gene, Vangl2, maintains apical‐basal organisation of the corneal epithelium

Abstract

The role of the core planar cell polarity (PCP) pathway protein, Vangl2, was investigated in the corneal epithelium of the mammalian eye, a paradigm anatomical model of planar cell migration. The gene was conditionally knocked out in vivo and knocked down by siRNA, followed by immunohistochemical, behavioural and morphological analysis of corneal epithelial cells. The primary defects observed in vivo were of apical-basal organisation of the corneal epithelium, with abnormal stratification throughout life, mislocalisation of the cell membrane protein, Scribble, to the basal side of cells, and partial loss of the epithelial basement membrane. Planar defects in migration after wounding and in the presence of an applied electric field were noted. However, knockdown of Vangl2 also retarded cell migration in individual cells that had no contact with their neighbours, which precluded a classic PCP mechanism. It is concluded that some of the planar polarity phenotypes in PCP mutants may arise from disruption of apical-basal polarity.

Transformation of the Transcriptomic Profile of Mouse Periocular Mesenchyme During Formation of the Embryonic Cornea

“…Fzd3 is involved in neural crest induction and migration 106–108. Reduced expression of Fzd4 and Fzd3 and upregulation of Fzd10 and Fzd6 may be required for corneal cell differentiation and avascularity 100–103,109–111. Despite upregulation of Wnt ligands and receptors, our data suggest that Wnt/β-catenin signaling is inhibited at multiple levels.…”

Disrupted endosomal trafficking of the Vangl-Celsr polarity complex underlies congenital anomalies in trachea-esophageal morphogenesis

“…Well known for their other roles in the planar cell polarity (PCP) pathway, in polarized epithelial cells Vangl2 and Celsr1 form heterotypic cell-cell complexes that localize to the apical cell surface (Butler and Wallingford, 2017) and are known to be internalized by endosomes during mitosis in the context of the developing epidermis (Devenport et al, 2011). Vangl2 can interact with and localize apical-basal polarity proteins in cell- and tissue-specific contexts, either by interacting with Scrib to restrict it to the basolateral domain (Panzica et al, 2019; vandenBerg and Sassoon, 2009) or by indirectly recruiting Par3 to the apical aPKC/Par complex (Aigouy and Le Bivic, 2016).…”

“…One candidate pathway that might regulate this process is the Vangl-Celsr polarity complex. In addition to their well-known role in the Wnt/PCP pathway where heterotypic cell-cell interactions between transmembrane Vangl, Celsr, and Frizzled proteins govern cell orientation in the plane of the epithelia 23 , Vangl and Celsr are also involved in specifying apical-basal polarity in epithelia by recruiting apical Par3 and aPKC whilst restricting Scrib to the basolateral domain 16,24,25 . Furthermore, apical Vangl-Celsr complexes are reported to be internalized by endosomes during polarized cell divisions of the fetal mouse epidermis 26 , suggesting a potential mechanistic link in the foregut.…”

Prickle1‐driven basement membrane deposition of the iPSC‐derived embryoid bodies is separable from the establishment of apicobasal polarity

“… 17 , 18 , 19 , 20 , 21 Whilst little is known about the connection between the classic AB modules and BM deposition, the PCP component, Vangl2, is crucial for BM integrity and localization of the mouse corneal epithelium. 22 Furthermore, the ascidian aimless ( aim ), encoding an ortholog protein of the vertebrate PCP component, Prickle, is reported to regulate Laminin protein localization during embryonic axis development. 10 Our recent study showed that disruption of Prickle1 completely abrogates BM formation of the tear duct epithelium, with altered cell–cell adhesion and cell axis orientation to some degrees.…”