Assessing PCP in the Cochlea of Mammalian Ciliopathy Models

Part of the Methods in Molecular Biology book series (MIMB, volume 839)

Abstract

The increased availability of mouse models of human genetic ciliary diseases has led to advances in our understanding of the diverse cellular roles played by cilia. The family of so-called “ciliopathies” includes Alström Syndrome, Bardet–Biedl Syndrome, Primary Ciliary Dyskinesia, and Polycystic Kidney Disease, among many others. In mouse models of Alström Syndrome and Bardet–Biedl Syndrome, we have shown developmental defects in the mechano-sensory stereociliary bundles on the apical surfaces of “hair” cells in the cochlea, the mammalian hearing organ. Stereocilia are specialized actin-based microvilli, whose characteristic patterning is thought to be dependent on the hair cell’s primary cilium (“kinocilium”). Ciliopathy-associated proteins are localized to the ciliary axoneme and/or the ciliary basal body, or to the bundle itself. Ciliopathy-associated genes functionally interact with genes of the noncanonical Wnt pathway, and so implicate PCP in the control of hair cell development.

Key words

Alström Syndrome Bardet–Biedl Syndrome Cilium Deafness Hair cells Kinocilium Organ of Corti Stereocilia 

Notes

Acknowledgments

The authors would like to thank Phil Beales (UCL) for Bbs mice, and David Wilson (University of Southampton) for the ALMS1 antibody. The Biotechnology and Biological Sciences Research Council and Deafness Research UK supported this work. DJ is a Royal Society University Research Fellow.

References

  1. 1.
    Forge, A., Wright, T.: The molecular architecture of the inner ear. Br Med Bull 63, 5–24 (2002).PubMedCrossRefGoogle Scholar
  2. 2.
    Gale, J.E., Jagger, D.J.: Cochlear supporting cells. In: Fuchs, P.A. (ed.) The Oxford Handbook of Auditory Science: The Ear. pp. 307–327. Oxford University Press, Oxford (2010).Google Scholar
  3. 3.
    Denman-Johnson, K., Forge, A.: Establishment of hair bundle polarity and orientation in the developing vestibular system of the mouse. J Neurocytol 28(10–11), 821–835 (1999).PubMedCrossRefGoogle Scholar
  4. 4.
    Nayak, G.D., Ratnayaka, H.S., Goodyear, R.J., Richardson, G.P.: Development of the hair bundle and mechanotransduction. Int J Dev Biol 51(6–7), 597–608 (2007). doi:072392gn [pii] 10.1387/ijdb.072392gn.PubMedCrossRefGoogle Scholar
  5. 5.
    Ross, A.J., May-Simera, H., Eichers, E.R., Kai, M., Hill, J., Jagger, D.J., Leitch, C.C., Chapple, J.P., Munro, P.M., Fisher, S., Tan, P.L., Phillips, H.M., Leroux, M.R., Henderson, D.J., Murdoch, J.N., Copp, A.J., Eliot, M.M., Lupski, J.R., Kemp, D.T., Dollfus, H., Tada, M., Katsanis, N., Forge, A., Beales, P.L.: Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates. Nat Genet 37(10), 1135–1140 (2005).PubMedCrossRefGoogle Scholar
  6. 6.
    Collin, G.B., Cyr, E., Bronson, R., Marshall, J.D., Gifford, E.J., Hicks, W., Murray, S.A., Zheng, Q.Y., Smith, R.S., Nishina, P.M., Naggert, J.K.: Alms1-disrupted mice recapitulate human Alstrom syndrome. Hum Mol Genet 14(16), 2323–2333 (2005).PubMedCrossRefGoogle Scholar
  7. 7.
    May-Simera, H.L., Ross, A., Rix, S., Forge, A., Beales, P.L., Jagger, D.J.: Patterns of expression of Bardet-Biedl syndrome proteins in the ­mammalian cochlea suggest noncentrosomal functions. J Comp Neurol 514(2), 174–188 (2009).PubMedCrossRefGoogle Scholar
  8. 8.
    Jagger, D., Collin, G., Kelly, J., Towers, E., Nevill, G., Longo-Guess, C., Benson, J., Halsey, K., Dolan, D., Marshall, J., Naggert, J., Forge, A.: Alstrom Syndrome protein ALMS1 localizes to basal bodies of cochlear hair cells and regulates cilium-dependent planar cell polarity. Hum Mol Genet 20(3), 466–481 (2011). doi:ddq493 [pii] 10.1093/hmg/ddq493.PubMedCrossRefGoogle Scholar
  9. 9.
    Jones, C., Chen, P.: Primary cilia in planar cell polarity regulation of the inner ear. Curr Top Dev Biol 85, 197–224 (2008).PubMedCrossRefGoogle Scholar
  10. 10.
    Hearn, T., Spalluto, C., Phillips, V.J., Renforth, G.L., Copin, N., Hanley, N.A., Wilson, D.I.: Subcellular localization of ALMS1 supports involvement of centrosome and basal body dysfunction in the pathogenesis of obesity, insulin resistance, and type 2 diabetes. Diabetes 54(5), 1581–1587 (2005).PubMedCrossRefGoogle Scholar
  11. 11.
    Davies, S., Forge, A.: Preparation of the mammalian organ of Corti for scanning electron microscopy. J Microsc 147(Pt 1), 89–101 (1987).PubMedCrossRefGoogle Scholar
  12. 12.
    Jagger, D.J., Forge, A.: Compartmentalized and signal-selective gap junctional coupling in the hearing cochlea. J Neurosci 26(4), ­1260–1268 (2006).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Centre for Auditory Research, UCL Ear InstituteUniversity College LondonLondonUK

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