title: Secreted frizzled-related protein disrupts PCP in eye lens fiber cells that have polarised primary cilia.
abstract: Planar cell polarity (PCP) signaling polarises cells along tissue axes. Although pathways involved are becoming better understood, outstanding issues include; (i) existence/identity of cues that orchestrate global polarisation in tissues, and (ii) the generality of the link between polarisation of primary cilia and asymmetric localisation of PCP proteins. Mammalian lenses are mainly comprised of epithelial-derived fiber cells. Concentrically arranged fibers are precisely aligned as they elongate along the anterior-posterior axis and orientate towards lens poles where they meet fibers from other segments to form characteristic sutures. We show that lens exhibits PCP, with each fiber cell having an apically situated cilium and in most cases this is polarised towards the anterior pole. Frizzled and other PCP proteins are also asymmetrically localised along the equatorial-anterior axis. Mutations in core PCP genes Van Gogh-like 2 and Celsr1 perturb oriented fiber alignment and suture formation. Suppression of the PCP pathway by overexpressing Sfrp2 shows that whilst local groups of fibers are often similarly oriented, they lack global orientation; consequently when local groups of fibers with different orientations meet they form multiple, small, ectopic suture-like configurations. This indicates that this extracellular inhibitor disrupts a global polarising signal that utilises a PCP-mediated mechanism to coordinate the global alignment and orientation of fibers to lens poles.
authors.affiliation: Save Sight Institute, The University of Sydney, NSW 2001, Australia.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: Richard J W
authors.initials: RJ
authors.lastname: Stump
authors.forename: Anke
authors.initials: A
authors.lastname: Nguyen
authors.forename: Li
authors.initials: L
authors.lastname: Wen
authors.forename: Yongjuan
authors.initials: Y
authors.lastname: Chen
authors.forename: Yanshu
authors.initials: Y
authors.lastname: Wang
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Murdoch
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Lovicu
authors.forename: John W
authors.initials: JW
authors.lastname: McAvoy
mesh_terms: D000818:Animals; D016764:Cell Polarity; D002923:Cilia / Q000648:ultrastructure*; D004847:Epithelial Cells / Q000737:chemistry / Q000473:pathology; D051157:Frizzled Receptors / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D007908:Lens, Crystalline / Q000166:cytology / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D000099274:Frizzled-Related Proteins; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D051157:Frizzled Receptors; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D043562:Receptors, G-Protein-Coupled; D000099274:Frizzled-Related Proteins; C117380:Celsr1 protein, mouse; C431577:Ltap protein, mouse; C491628:Sfrp2 protein, mouse; D000094742:Secreted Frizzled-Related Proteins