Nature Genetics
37, 1135 - 1140 (2005)
Published online: 18 September 2005; | doi:10.1038/ng1644
Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebratesAlison J Ross1, 13, Helen May-Simera1, 13, Erica R Eichers2, Masatake Kai3, Josephine Hill1, Daniel J Jagger4, Carmen C Leitch5, J Paul Chapple6, Peter M Munro6, Shannon Fisher5, Perciliz L Tan5, Helen M Phillips7, Michel R Leroux8, Deborah J Henderson7, Jennifer N Murdoch9, Andrew J Copp10, Marie-Madeleine Eliot11, James R Lupski2, David T Kemp4, Hélène Dollfus12, Masazumi Tada3, Nicholas Katsanis5, Andrew Forge4
& Philip L Beales11
Molecular Medicine Unit, Institute of Child Health, University College London, WC1N 1EH, UK. 2
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA. 3
Department of Anatomy and Developmental Biology, University College London, WC1E 6BT, UK. 4
Centre for Auditory Research, The Ear Institute, University College London, UK. 5
Institute of Genetic Medicine, Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland 21287, USA. 6
Institute of Ophthalmology, University College London, EC1V 9EL, UK. 7
Institute of Human Genetics, University of Newcastle upon Tyne, UK. 8
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada. 9
MRC Mammalian Genetics Unit, Harwell, UK. 10
Neural Development Unit, Institute of Child Health, University College London WC1N 1EH, UK. 11
Service d'ORL, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. 12
Service de Génétique Médicale, Hôpitaux Universitaires de Strasbourg; Laboratoire de Génétique Médicale, Faculté de Médecine, Université Louis Pasteur de Strasbourg, Strasbourg, France. 13
These authors contributed equally to this work.
Correspondence should be addressed to Philip L Beales p.beales@ucl.ac.uk 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 orientation1. In vertebrates, PCP genes have a vital role in polarized convergent extension movements during gastrulation and neurulation2. Here we show that mice with mutations in genes involved in Bardet-Biedl syndrome (BBS), a disorder associated with ciliary dysfunction3,
4, 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.
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated.
|
