title: Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates.
abstract: The evolutionarily conserved planar cell polarity (PCP) pathway (or noncanonical Wnt pathway) drives several important cellular processes, including epithelial cell polarization, cell migration and mitotic spindle orientation. In vertebrates, PCP genes have a vital role in polarized convergent extension movements during gastrulation and neurulation. Here we show that mice with mutations in genes involved in Bardet-Biedl syndrome (BBS), a disorder associated with ciliary dysfunction, share phenotypes with PCP mutants including open eyelids, neural tube defects and disrupted cochlear stereociliary bundles. Furthermore, we identify genetic interactions between BBS genes and a PCP gene in both mouse (Ltap, also called Vangl2) and zebrafish (vangl2). In zebrafish, the augmented phenotype results from enhanced defective convergent extension movements. We also show that Vangl2 localizes to the basal body and axoneme of ciliated cells, a pattern reminiscent of that of the BBS proteins. These data suggest that cilia are intrinsically involved in PCP processes.
authors.affiliation: Molecular Medicine Unit, Institute of Child Health, University College London, WC1N 1EH, UK.
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Ross
authors.forename: Helen
authors.initials: H
authors.lastname: May-Simera
authors.forename: Erica R
authors.initials: ER
authors.lastname: Eichers
authors.forename: Masatake
authors.initials: M
authors.lastname: Kai
authors.forename: Josephine
authors.initials: J
authors.lastname: Hill
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Jagger
authors.forename: Carmen C
authors.initials: CC
authors.lastname: Leitch
authors.forename: J Paul
authors.initials: JP
authors.lastname: Chapple
authors.forename: Peter M
authors.initials: PM
authors.lastname: Munro
authors.forename: Shannon
authors.initials: S
authors.lastname: Fisher
authors.forename: Perciliz L
authors.initials: PL
authors.lastname: Tan
authors.forename: Helen M
authors.initials: HM
authors.lastname: Phillips
authors.forename: Michel R
authors.initials: MR
authors.lastname: Leroux
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Henderson
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Murdoch
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Copp
authors.forename: Marie-Madeleine
authors.initials: MM
authors.lastname: Eliot
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
authors.forename: David T
authors.initials: DT
authors.lastname: Kemp
authors.forename: Hélène
authors.initials: H
authors.lastname: Dollfus
authors.forename: Masazumi
authors.initials: M
authors.lastname: Tada
authors.forename: Nicholas
authors.initials: N
authors.lastname: Katsanis
authors.forename: Andrew
authors.initials: A
authors.lastname: Forge
authors.forename: Philip L
authors.initials: PL
authors.lastname: Beales
mesh_terms: D000818:Animals; D020788:Bardet-Biedl Syndrome / Q000235:genetics / Q000473:pathology*; D016764:Cell Polarity / Q000235:genetics; D002923:Cilia / Q000737:chemistry; D003051:Cochlea / Q000473:pathology; D004847:Epithelial Cells / Q000737:chemistry; D005143:Eyelids / Q000503:physiopathology; D056385:Group II Chaperonins; D051379:Mice; D008817:Mice, Mutant Strains; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D018832:Molecular Chaperones / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism*; D009436:Neural Tube Defects / Q000473:pathology; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism
chemical_list: C506281:BBS4 protein, mouse; C506280:Bbs1 protein, mouse; C431577:Ltap protein, mouse; D008869:Microtubule-Associated Proteins; C506279:Mkks protein, mouse; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D056385:Group II Chaperonins