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

被引:458
作者
Ross, AJ
May-Simera, H
Eichers, ER
Kai, M
Hill, J
Jagger, DJ
Leitch, CC
Chapple, JP
Munro, PM
Fisher, S
Tan, PL
Phillips, HM
Leroux, MR
Henderson, DJ
Murdoch, JN
Copp, AJ
Eliot, MM
Lupski, JR
Kemp, DT
Dollfus, H
Tada, M
Katsanis, N
Forge, A
Beales, PL
机构
[1] UCL, Inst Child Hlth, Mol Med Unit, London WC1N 1EH, England
[2] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA
[3] UCL, Dept Anat & Dev Biol, London WC1E 6BT, England
[4] UCL, Ear Inst, Ctr Auditory Res, London WC1E 6BT, England
[5] Johns Hopkins Univ, Wilmer Eye Inst, Inst Med Genet, Baltimore, MD 21287 USA
[6] UCL, Inst Ophthalmol, London EC1V 9EL, England
[7] Univ Newcastle Upon Tyne, Inst Human Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
[8] Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada
[9] MRC Mammalian Genet Unit, Harwell, Berks, England
[10] UCL, Inst Child Hlth, Neural Dev Unit, London WC1N 1EH, England
[11] Hop Univ Strasbourg, Serv ORL, Strasbourg, France
[12] Hop Univ Strasbourg, Serv Genet Med, Strasbourg, France
[13] Univ Strasbourg 1, Fac Med, Med Genet Lab, Strasbourg, France
基金
英国惠康基金;
关键词
D O I
10.1038/ng1644
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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(1). In vertebrates, PCP genes have a vital role in polarized convergent extension movements during gastrulation and neurulation(2). Here we show that mice with mutations in genes involved in Bardet-Biedl syndrome (BBS), a disorder associated with ciliary dysfunction(3,4), 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.
引用
收藏
页码:1135 / 1140
页数:6
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