title: Duplicated genes with split functions: independent roles of protocadherin15 orthologues in zebrafish hearing and vision.
abstract: 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.
authors.affiliation: Max Planck Institut fur Entwicklungsbiologie, Spemannstrasse 35, 72076 Tübingen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Seiler
authors.forename: Karin C
authors.initials: KC
authors.lastname: Finger-Baier
authors.forename: Oliver
authors.initials: O
authors.lastname: Rinner
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Makhankov
authors.forename: Heinz
authors.initials: H
authors.lastname: Schwarz
authors.forename: Stephan C F
authors.initials: SC
authors.lastname: Neuhauss
authors.forename: Teresa
authors.initials: T
authors.lastname: Nicolson
mesh_terms: D000818:Animals; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism*; D004594:Electrophysiology; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism*; D020440:Gene Duplication; D018507:Gene Expression Regulation, Developmental; D020131:Genes, Duplicate / Q000235:genetics*; D006309:Hearing / Q000235:genetics / Q000502:physiology*; D008854:Microscopy, Electron; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D010786:Photoreceptor Cells / Q000166:cytology / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D012160:Retina / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D012680:Sensitivity and Specificity; D014785:Vision, Ocular / Q000235:genetics / Q000502:physiology*; D015027:Zebrafish / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C497421:CDHR15 protein, zebrafish; D000070585:Cadherin Related Proteins; D015820:Cadherins; D029941:Fish Proteins; D029961:Zebrafish Proteins; C070896:M-cadherin