Duplicated genes with split functions

Independent roles of protocadherin 15 orthologues in zebrafish hearing and vision

Christoph Seiler, Karin C. Finger-Baier, Oliver Rinner, Yuri V. Makhankov, Heinz Schwarz, Stephan C F Neuhauss, Teresa Nicolson

Research output: Contribution to journalArticle

90 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)615-623
Number of pages9
JournalDevelopment
Volume132
Issue number3
DOIs
StatePublished - Feb 2005

Fingerprint

Zebrafish
Hearing
Ear
Morpholinos
Genes
Mutation
Retinal Pigment Epithelium
Antisense Oligonucleotides
Essential Genes
Deafness
Sensory Receptor Cells
Inner Ear
Cadherins
Acoustics
Organelles
Larva
Epithelium
Electrons
Light

Keywords

  • Blindness
  • Deafness
  • Gene duplication
  • Hair cell
  • orbiter
  • Outer segment
  • Photoreceptor
  • Protocadherin 15
  • Stereocilia
  • Zebrafish

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Seiler, C., Finger-Baier, K. C., Rinner, O., Makhankov, Y. V., Schwarz, H., Neuhauss, S. C. F., & Nicolson, T. (2005). Duplicated genes with split functions: Independent roles of protocadherin 15 orthologues in zebrafish hearing and vision. Development, 132(3), 615-623. https://doi.org/10.1242/dev.01591

Duplicated genes with split functions : Independent roles of protocadherin 15 orthologues in zebrafish hearing and vision. / Seiler, Christoph; Finger-Baier, Karin C.; Rinner, Oliver; Makhankov, Yuri V.; Schwarz, Heinz; Neuhauss, Stephan C F; Nicolson, Teresa.

In: Development, Vol. 132, No. 3, 02.2005, p. 615-623.

Research output: Contribution to journalArticle

Seiler, C, Finger-Baier, KC, Rinner, O, Makhankov, YV, Schwarz, H, Neuhauss, SCF & Nicolson, T 2005, 'Duplicated genes with split functions: Independent roles of protocadherin 15 orthologues in zebrafish hearing and vision', Development, vol. 132, no. 3, pp. 615-623. https://doi.org/10.1242/dev.01591
Seiler C, Finger-Baier KC, Rinner O, Makhankov YV, Schwarz H, Neuhauss SCF et al. Duplicated genes with split functions: Independent roles of protocadherin 15 orthologues in zebrafish hearing and vision. Development. 2005 Feb;132(3):615-623. https://doi.org/10.1242/dev.01591
Seiler, Christoph ; Finger-Baier, Karin C. ; Rinner, Oliver ; Makhankov, Yuri V. ; Schwarz, Heinz ; Neuhauss, Stephan C F ; Nicolson, Teresa. / Duplicated genes with split functions : Independent roles of protocadherin 15 orthologues in zebrafish hearing and vision. In: Development. 2005 ; Vol. 132, No. 3. pp. 615-623.
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