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Ciliary proteins link basal body polarization to planar cell polarity regulation

Nature Genetics volume 40, pages 69–77 (2008)Cite this article

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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Figure 1: Ift88 is expressed in primary cilia in the organ of Corti.
Figure 2: Misorientation of stereociliary bundles in Ift88 mutants.
Figure 3: Ift88 is required for cochlear extension.
Figure 4: PCP complexes are partitioned normally in Ift88 mutants.
Figure 5: Ciliary basal body positions are affected in Ift88 mutants.
Figure 6: Alteration of the apical cytoskeleton in Ift88 mutants.
Figure 7: Model of the role of ciliary genes and cilia in centriole and morphological polarization during the establishment of PCP in the organ of Corti.

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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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Authors and Affiliations

  1. Department of Cell Biology, Emory University School of Medicine, 615 Michael St., Atlanta, Georgia 30322, USA.,

    Chonnettia Jones, Dong Qian & Ping Chen

  2. Department of Cell Biology, University of Alabama, Birmingham, 35294, Alabama, USA

    Venus C Roper, Boglarka Banizs & Bradley K Yoder

  3. Institut national de la santé et de la recherche médicale (INSERM) UMRS 587, Unité de Génétique des Déficits Sensoriels, Collège de France, Institut Pasteur, Paris, 75724, France

    Isabelle Foucher & Christine Petit

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Contributions

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.

Corresponding author

Correspondence to Ping Chen.

Supplementary information

Supplementary Text and Figures

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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