Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Regulation of polarized extension and planar cell polarity in the cochlea by the vertebrate PCP pathway


The mammalian auditory sensory organ, the organ of Corti, consists of sensory hair cells with uniformly oriented stereocilia on the apical surfaces and has a distinct planar cell polarity (PCP) parallel to the sensory epithelium1,2,3. It is not certain how this polarity is achieved during differentiation4,5. Here we show that the organ of Corti is formed from a thicker and shorter postmitotic primordium through unidirectional extension, characteristic of cellular intercalation known as convergent extension6. Mutations in the PCP pathway interfere with this extension, resulting a shorter and wider cochlea as well as misorientation of stereocilia. Furthermore, parallel to the homologous pathway in Drosophila melanogaster7,8, a mammalian PCP component Dishevelled2 shows PCP-dependent polarized subcellular localization across the organ of Corti. Taken together, these data suggest that there is a conserved molecular mechanism for PCP pathways in invertebrates and vertebrates and indicate that the mammalian PCP pathway might directly couple cellular intercalations to PCP establishment in the cochlea.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Differentiation of the organ of Corti from its postmitotic precursor domain.
Figure 2: Unidirectional extension of the organ of Corti in vitro.
Figure 3: Presence of a functional PCP pathway in the developing organ of Corti.
Figure 4: The stereocilia of the organ of Corti had abnormal polarity in Dvl DKO, Lp/Lp and Dvl2−/− Lp/+ embryos.
Figure 5: Shorter and wider cochlear duct and its sensory organ in PCP mutants.
Figure 6: Direct requirement for PCP pathway in extension and PCP of the organ of Corti.

Accession codes




  1. Montcouquiol, M. et al. Identification of Vangl2 and Scrb1 as planar polarity genes in mammals. Nature 423, 173–177 (2003).

    Article  CAS  Google Scholar 

  2. Curtin, J.A. et al. Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse. Curr. Biol. 13, 1129–1133 (2003).

    Article  CAS  Google Scholar 

  3. Lu, X. et al. PTK7/CCK-4 is a novel regulator of planar cell polarity in vertebrates. Nature 430, 93–98 (2004).

    Article  CAS  Google Scholar 

  4. Chen, P., Johnson, J.E., Zoghbi, H.Y. & Segil, N. The role of Math1 in inner ear development: Uncoupling the establishment of the sensory primordium from hair cell fate determination. Development 129, 2495–2505 (2002).

    Article  CAS  Google Scholar 

  5. Lewis, J. & Davies, A. Planar cell polarity in the inner ear: how do hair cells acquire their oriented structure? J. Neurobiol. 53, 190–201 (2002).

    Article  CAS  Google Scholar 

  6. Keller, R. Shaping the vertebrate body plan by polarized embryonic cell movements. Science 298, 1950–1954 (2002).

    Article  CAS  Google Scholar 

  7. Axelrod, J.D. Unipolar membrane association of Dishevelled mediates Frizzled planar cell polarity signaling. Genes Dev. 15, 1182–1187 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Bastock, R., Strutt, H. & Strutt, D. Strabismus is asymmetrically localized and binds to Prickle and Dishevelled during Drosophila planar polarity patterning. Development 130, 3007–3014 (2003).

    Article  CAS  Google Scholar 

  9. Ruben, R.J. Development of the inner ear of the mouse: a radioautographic study of terminal mitoses. Acta Otolaryngol. (Stockh.) Supp. 220, 1–44 (1967).

    Google Scholar 

  10. Chen, P. & Segil, N. p27(Kip1) links cell proliferation to morphogenesis in the developing organ of Corti. Development 126, 1581–1590 (1999).

    CAS  Google Scholar 

  11. McKenzie, E., Krupin, A. & Kelley, M.W. Cellular growth and rearrangement during the development of the mammalian organ of Corti. Dev. Dyn. 229, 802–812 (2004).

    Article  CAS  Google Scholar 

  12. Vinson, C.R. & Adler, P.N. Directional non-cell autonomy and the transmission of polarity information by the frizzled gene of Drosophila. Nature 329, 549–551 (1987).

    Article  CAS  Google Scholar 

  13. Mlodzik, M. Planar cell polarization: do the same mechanisms regulate Drosophila tissue polarity and vertebrate gastrulation? Trends Genet. 18, 564–571 (2002).

    Article  CAS  Google Scholar 

  14. Ma, D., Yang, C.H., McNeill, H., Simon, M.A. & Axelrod, J.D. Fidelity in planar cell polarity signalling. Nature 421, 543–547 (2003).

    Article  CAS  Google Scholar 

  15. Tree, D.R., Ma, D. & Axelrod, J.D. A three-tiered mechanism for regulation of planar cell polarity. Semin. Cell Dev. Biol. 13, 217–224 (2002).

    Article  CAS  Google Scholar 

  16. Kibar, Z. et al. Ltap, a mammalian homolog of Drosophila Strabismus/Van Gogh, is altered in the mouse neural tube mutant Loop-tail. Nat. Genet. 28, 251–255 (2001).

    Article  CAS  Google Scholar 

  17. Chae, J. et al. The Drosophila tissue polarity gene starry night encodes a member of the protocadherin family. Development 126, 5421–5429 (1999).

    CAS  PubMed  Google Scholar 

  18. Usui, T. et al. Flamingo, a seven-pass transmembrane cadherin, regulates planar cell polarity under the control of Frizzled. Cell 98, 585–595 (1999).

    Article  CAS  Google Scholar 

  19. Lijam, N. et al. Social interaction and sensorimotor gating abnormalities in mice lacking Dvl1. Cell 90, 895–905 (1997).

    Article  CAS  Google Scholar 

  20. Hamblet, N.S. et al. Dishevelled 2 is essential for cardiac outflow tract development, somite segmentation and neural tube closure. Development 129, 5827–5838 (2002).

    Article  CAS  Google Scholar 

  21. Darken, R.S. et al. The planar polarity gene strabismus regulates convergent extension movements in Xenopus. EMBO J. 21, 976–985 (2002).

    Article  CAS  Google Scholar 

  22. Goto, T. & Keller, R. The planar cell polarity gene strabismus regulates convergence and extension and neural fold closure in Xenopus. Dev. Biol. 247, 165–181 (2002).

    Article  CAS  Google Scholar 

  23. Wallingford, J.B. et al. Dishevelled controls cell polarity during Xenopus gastrulation. Nature 405, 81–85 (2000).

    Article  CAS  Google Scholar 

  24. Wallingford, J.B. & Harland, R.M. Neural tube closure requires Dishevelled-dependent convergent extension of the midline. Development 129, 5815–5825 (2002).

    Article  CAS  Google Scholar 

  25. Axelrod, J.D., Miller, J.R., Shulman, J.M., Moon, R.T. & Perrimon, N. Differential recruitment of dishevelled provides signaling specificity in the planar cell polarity and wingless signaling pathways. Genes Dev. 12, 2610–2622 (1998).

    Article  CAS  Google Scholar 

  26. Boutros, M., Paricio, N., Strutt, D.I. & Mlodzik, M. Dishevelled activates JNK and discriminates between JNK pathways in planar polarity and wingless signaling. Cell 94, 109–118 (1998).

    Article  CAS  Google Scholar 

  27. Torban, E., Wang, H.J., Groulx, N. & Gros, P. Independent mutations in mouse Vangl2 that cause neural tube defects in looptail mice impair interaction with members of the Dishevelled family. J. Biol. Chem. 279, 52703–52713 (2004).

    Article  CAS  Google Scholar 

  28. Kelley, M.W., Xu, X.M., Wagner, M.A., Warchol, M.E. & Corwin, J.T. The developing organ of Corti contains retinoic acid and forms supernumerary hair cells in response to exogenous retinoic acid in culture. Development 119, 1041–1053 (1993).

    CAS  PubMed  Google Scholar 

  29. Jiang, D., Munro, E.M. & Smith, W.C. Ascidian prickle regulates both mediolateral and anterior-posterior cell polarity of notochord cells. Curr. Biol. 15, 79–85 (2005).

    Article  CAS  Google Scholar 

  30. Radde-Gallwitz, K. et al. Expression of Islet 1 marks the sensory and neuronal lineages in the mammalian inner ear. J. Comp. Neurol. 477, 412–421 (2004).

    Article  CAS  Google Scholar 

Download references


We thank K. Moses, W. Sale, B. Shur and J. Wallingford for discussions during the project and comments on the manuscript; D. Martin, T. Etzel, E. Kothari and J. Zhao for transgenic service; D. Wu for technical advice on inner ear paint fill; R. Apkarian for SEM; J. Saek for hair cell counting; J.E. Johnson for Math1GFP animals; W. Sale for acetylated α-tubulin antibody; the UCSD/NINDS Neuroscience Microscopy Core; and the Developmental Studies Hybridoma Bank for Islet1 antibody. This work is supported by grants from the US National Institute of Health (to A.C., X.L., A.W.-B. and P.C.), the Woodruff Foundation (to X.L. and P.C.) and the American Heart Association (to J.W.).

Author information

Authors and Affiliations


Corresponding authors

Correspondence to Anthony Wynshaw-Boris or Ping Chen.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Unidirectional extension of the cochlea and its sensory organ by DiI labeling in vitro. (PDF 65 kb)

Supplementary Fig. 2

Generation of transgenic mice carrying Dvl2-EGFP. (PDF 315 kb)

Supplementary Fig. 3

Postulated radial and medial-lateral intercalation of the organ of Corti during terminal differentiation. (PDF 109 kb)

Supplementary Table 1

Tabulation of decreased length to width ration and hair cell numbers in PCP mutants. (PDF 100 kb)

Supplementary Table 2

Primers used for genotyping and cDNA amplification. (PDF 32 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Wang, J., Mark, S., Zhang, X. et al. Regulation of polarized extension and planar cell polarity in the cochlea by the vertebrate PCP pathway. Nat Genet 37, 980–985 (2005).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing