Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates

Nat Genet. 2005 Oct;37(10):1135-40. doi: 10.1038/ng1644.

Alison J Ross ¹, Helen May-Simera, Erica R Eichers, Masatake Kai, Josephine Hill, Daniel J Jagger, Carmen C Leitch, J Paul Chapple, Peter M Munro, Shannon Fisher, Perciliz L Tan, Helen M Phillips, Michel R Leroux, Deborah J Henderson, Jennifer N Murdoch, Andrew J Copp, Marie-Madeleine Eliot, James R Lupski, David T Kemp, Hélène Dollfus, Masazumi Tada, Nicholas Katsanis, Andrew Forge, Philip L Beales

Affiliations

Affiliation

1 Molecular Medicine Unit, Institute of Child Health, University College London, WC1N 1EH, UK.

PMID: 16170314 DOI: 10.1038/ng1644

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.

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