QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 5 January 2005
doi: 10.1242/dev.01591

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: dev.01591v1 132/3/615    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Seiler, C. Articles by Nicolson, T. Search for Related Content PubMed PubMed Citation Articles by Seiler, C. Articles by Nicolson, T. Social Bookmarking                         What's this?

Duplicated genes with split functions: independent roles of protocadherin15 orthologues in zebrafish hearing and vision

¹ Max Planck Institut fur Entwicklungsbiologie, Spemannstrasse 35, 72076 Tübingen, Germany
² Brain Research Institute, University of Zurich and Department of Biology, Swiss Federal Institute of Technology Zurich, Winterthurerstr. 190 8057 Zurich, Switzerland
³ Oregon Hearing Research Center and Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA

^* Author for correspondence (e-mail: nicolson{at}ohsu.edu)

Accepted 23 November 2004

In the sensory receptors of both the eye and the ear, specialized apical structures have evolved to detect environmental stimuli such as light and sound. Despite the morphological divergence of these specialized structures and differing transduction mechanisms, the receptors appear to rely in part on a shared group of genes for function. For example, mutations in Usher (USH) genes cause a syndrome of visual and acoustic-vestibular deficits in humans. Several of the affected genes have been identified, including the USH1F gene, which encodes protocadherin 15 (PCDH15). Pcdh15 mutant mice also have both auditory and vestibular defects, although visual defects are not evident. Here we show that zebrafish have two closely related pcdh15 genes that are required for receptor-cell function and morphology in the eye or ear. Mutations in pcdh15a cause deafness and vestibular dysfunction, presumably because hair bundles of inner-ear receptors are splayed. Vision, however, is not affected in pcdh15a mutants. By contrast, reduction of pcdh15b activity using antisense morpholino oligonucleotides causes a visual defect. Optokinetic and electroretinogram responses are reduced in pcdh15b morpholino-injected larvae. In electron micrographs, morphant photoreceptor outer segments are improperly arranged, positioned perpendicular to the retinal pigment epithelium and are clumped together. Our results suggest that both cadherins act within their respective transduction organelles: Pcdh15a is necessary for integrity of the stereociliary bundle, whereas Pcdh15b is required for alignment and interdigitation of photoreceptor outer segments with the pigment epithelium. We conclude that after a duplication of pcdh15, one gene retained an essential function in the ear and the other in the eye.

Key words: Protocadherin 15, Hair cell, Photoreceptor, Zebrafish, Deafness, Blindness, Outer segment, Stereocilia, Gene duplication, orbiter

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

Related articles in Development:

protocadherin15 links sight and sound

Development 2005 132: e306. [Full Text]  

This article has been cited by other articles:

				M. Tanimoto, Y. Ota, K. Horikawa, and Y. Oda Auditory Input to CNS Is Acquired Coincidentally with Development of Inner Ear after Formation of Functional Afferent Pathway in Zebrafish J. Neurosci., March 4, 2009; 29(9): 2762 - 2767. [Abstract] [Full Text] [PDF]

				N. A. Ramakrishnan, M. J. Drescher, R. L. Barretto, K. W. Beisel, J. S. Hatfield, and D. G. Drescher Calcium-dependent Binding of HCN1 Channel Protein to Hair Cell Stereociliary Tip Link Protein Protocadherin 15 CD3 J. Biol. Chem., January 30, 2009; 284(5): 3227 - 3238. [Abstract] [Full Text] [PDF]

				Z.-L. Wang, X.-P. Xu, B.-L. He, S.-P. Weng, J. Xiao, L. Wang, T. Lin, X. Liu, Q. Wang, X.-Q. Yu, et al. Infectious Spleen and Kidney Necrosis Virus ORF48R Functions as a New Viral Vascular Endothelial Growth Factor J. Virol., May 1, 2008; 82(9): 4371 - 4383. [Abstract] [Full Text] [PDF]

				R. J. L. Haywood-Watson II, Z. M. Ahmed, S. Kjellstrom, R. A. Bush, Y. Takada, L. L. Hampton, J. F. Battey, P. A. Sieving, and T. B. Friedman Ames waltzer deaf mice have reduced electroretinogram amplitudes and complex alternative splicing of pcdh15 transcripts. Invest. Ophthalmol. Vis. Sci., July 1, 2006; 47(7): 3074 - 3084. [Abstract] [Full Text] [PDF]

				Z. M. Ahmed, R. Goodyear, S. Riazuddin, A. Lagziel, P. K. Legan, M. Behra, S. M. Burgess, K. S. Lilley, E. R. Wilcox, S. Riazuddin, et al. The tip-link antigen, a protein associated with the transduction complex of sensory hair cells, is protocadherin-15. J. Neurosci., June 28, 2006; 26(26): 7022 - 7034. [Abstract] [Full Text] [PDF]

				K. Schlichting, M. Wilsch-Brauninger, F. Demontis, and C. Dahmann Cadherin Cad99C is required for normal microvilli morphology in Drosophila follicle cells J. Cell Sci., March 15, 2006; 119(6): 1184 - 1195. [Abstract] [Full Text] [PDF]

				C. D'Alterio, D. D.D. Tran, M. W.Y. A. Yeung, M. S.H. Hwang, M. A. Li, C. J. Arana, V. K. Mulligan, M. Kubesh, P. Sharma, M. Chase, et al. Drosophila melanogaster Cad99C, the orthologue of human Usher cadherin PCDH15, regulates the length of microvilli J. Cell Biol., November 7, 2005; 171(3): 549 - 558. [Abstract] [Full Text] [PDF]

				A. El-Amraoui and C. Petit Usher I syndrome: unravelling the mechanisms that underlie the cohesion of the growing hair bundle in inner ear sensory cells J. Cell Sci., October 15, 2005; 118(20): 4593 - 4603. [Abstract] [Full Text] [PDF]