Abstract
Planar cell polarity (PCP) refers to coordinated polarization of cells within the plane of a cell sheet. A conserved signaling pathway is required for the establishment of PCP in epithelial tissues and for polarized cellular rearrangements known as convergent extension. During PCP signaling, core PCP proteins are sorted asymmetrically along the polarization axis; this sorting is thought to direct coordinated downstream morphogenetic changes across the entire tissue. Here, we show that a gene encoding a ciliary protein (a 'ciliary gene'), Ift88, also known as Polaris, is required for establishing epithelial PCP and for convergent extension of the cochlear duct of Mus musculus. We also show that the proper positioning of ciliary basal bodies and the formation of polarized cellular structures are disrupted in mice with mutant ciliary proteins ('ciliary mutants'), whereas core PCP proteins are partitioned normally along the polarization axis. Thus, our data uncover a distinct requirement for ciliary genes in basal body positioning and morphological polarization during PCP regulation.
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Acknowledgements
We thank W. Sale for discussions about the project, B. Shur, A. Fritz and T. Caspary for critical comments on the manuscript and S. Mark for technical support. We also thank S. Guadagnini and M.-C. Prévost from the Electron Microscopy Group (PFME) at the Pasteur Institute for their technical advice. Antibody against Fzd3 was a gift from J. Nathans (Johns Hopkins). This project is supported by NIH research grants to P.C. (RO1 DC005213 and DC007423) and B.K.Y. (RO1 DK065655), a postdoctoral fellowship to C.J. (F32DC008731), a Woodruff Foundation grant to P.C., a postdoctoral fellowship to I.F. (INSERM) and grants from Fondation R. & G. Strittmatter and from Ernst-Jung Stiftung für Medizin to C.P.
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C.J. carried out most of the analysis and played a pivotal role in progressively designing the experiments. V.C.R. and B.B. prepared Ift88flox/floxCreER and Kif3aflox/floxCreER samples. I.F. and C.P. contributed electron microscopy data. The study was initiated by B.K.Y and P.C., and carried out under the direction of P.C. C.J. and P.C. wrote the manuscript, which was critically commented upon and revised by B.K.Y. and C.P. D.Q. generated Vangl2GFP animals.
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Supplementary Figures 1–5 (PDF 730 kb)
Supplementary Video 1
Three-dimensional images of cellular microtubules in a wild-type cochlea. Images of the cellular microtubules from three outer hair cells in a wild-type cochlea were acquired using the Zeiss LSM510 confocal microscope, as described in the text (Fig. 6). Serial 0.5μm optical sections were acquired from the apical-most cell surface moving basally through the organ of corti and projected into three dimensions using NIH ImageJ software. This video complements Figure 6 and provides a more complete view of the apical microtubules. (MOV 43 kb)
Supplementary Video 2
Three-dimensional images of cellular microtubules in an IFT88CKO/CKO mutant cochlea. Images of the cellular microtubules from three outer hair cells in an IFT88CKO/CKO mutant cochlea were acquired using the Zeiss LSM510 confocal microscope, as described in the text (Fig. 6). Serial 0.5μm optical sections were acquired from the apical-most cell surface moving basally through the organ of corti and projected into three dimensions using NIH ImageJ software. This video complements Figure 6 and provides a more complete view of the apical microtubules. (MOV 89 kb)
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Jones, C., Roper, V., Foucher, I. et al. Ciliary proteins link basal body polarization to planar cell polarity regulation. Nat Genet 40, 69–77 (2008). https://doi.org/10.1038/ng.2007.54
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DOI: https://doi.org/10.1038/ng.2007.54
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