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Vangl2 directs the posterior tilting and asymmetric localization of motile primary cilia.

Nature cell biology | Apr 2, 2010

http://www.ncbi.nlm.nih.gov/pubmed/20305649

Cilia are microtubule-based organelles that project into the extracellular space, function in the perception and integration of environmental cues, and regulate Hedgehog signal transduction. The emergent association of ciliary defects with diverse and pleiotropic human disorders has fuelled investigations into the molecular genetic regulation of ciliogenesis. Although recent studies implicate planar cell polarity (PCP) in cilia formation, this conclusion is based on analyses of proteins that are not specific to, or downstream effectors of PCP signal transduction. Here we characterize zebrafish embryos devoid of all Vangl2 function, a core and specific component of the PCP signalling pathway. Using Arl13b-GFP as a live marker of the ciliary axoneme, we demonstrate that Vangl2 is not required for ciliogenesis. Instead, Vangl2 controls the posterior tilting of primary motile cilia lining the neurocoel, Kupffer's vesicle and pronephric duct. Furthermore, we show that Vangl2 is required for asymmetric localization of cilia to the posterior apical membrane of neuroepithelial cells. Our results indicate a broad and essential role for PCP in the asymmetric localization and orientation of motile primary cilia, establishing directional fluid flow implicated in normal embryonic development and disease.

Pubmed ID: 20305649 RIS Download

Mesh terms: ADP-Ribosylation Factors | Animals | Animals, Genetically Modified | Cell Polarity | Cilia | Embryo, Nonmammalian | Gene Expression Regulation, Developmental | Gene Knockout Techniques | Heparan Sulfate Proteoglycans | Membrane Proteins | Mice | Motion | Neuroepithelial Cells | Recombinant Fusion Proteins | Signal Transduction | Zebrafish | Zebrafish Proteins

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ZFIN (Data, Gene Expression)

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