The zebrafish dog-eared mutation disrupts eya1, a gene required for cell survival and differentiation in the inner ear and lateral line

David J Kozlowski, Tanya T. Whitfield, Neil A. Hukriede, Wai K. Lam, Eric S. Weinberg

Research output: Contribution to journalArticle

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Abstract

To understand the molecular basis of sensory organ development and disease, we have cloned and characterized the zebrafish mutation dog-eared (dog) that is defective in formation of the inner ear and lateral line sensory systems. The dog locus encodes the eyes absent-1 (eya1) gene and single point mutations were found in three independent dog alleles, each prematurely truncating the expressed protein within the Eya domain. Moreover, morpholino-mediated knockdown of eya1 gene function phenocopies the dog-eared mutation. In zebrafish, the eya1 gene is widely expressed in placode-derived sensory organs during embryogenesis but Eya1 function appears to be primarily required for survival of sensory hair cells in the developing ear and lateral line neuromasts. Increased levels of apoptosis occur in the migrating primordia of the posterior lateral line in dog embryos and as well as in regions of the developing otocyst that are mainly fated to give rise to sensory cells of the cristae. Importantly, mutation of the EYA1 or EYA4 gene causes hereditary syndromic deafness in humans. Determination of eya gene function during zebrafish organogenesis will facilitate understanding the molecular etiology of human vestibular and hearing disorders.

Original languageEnglish (US)
Pages (from-to)27-41
Number of pages15
JournalDevelopmental Biology
Volume277
Issue number1
DOIs
StatePublished - Jan 1 2005

Fingerprint

Zebrafish
Inner Ear
Cell Differentiation
Cell Survival
Mutation
Dogs
Genes
Lateral Line System
Hearing Disorders
Morpholinos
Organogenesis
Deafness
Point Mutation
Hair
Embryonic Development
Ear
Embryonic Structures
Alleles
Apoptosis
Proteins

Keywords

  • bmp4
  • Cristae
  • eya1
  • Fate mapping
  • Otic vesicle
  • Zebrafish

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

The zebrafish dog-eared mutation disrupts eya1, a gene required for cell survival and differentiation in the inner ear and lateral line. / Kozlowski, David J; Whitfield, Tanya T.; Hukriede, Neil A.; Lam, Wai K.; Weinberg, Eric S.

In: Developmental Biology, Vol. 277, No. 1, 01.01.2005, p. 27-41.

Research output: Contribution to journalArticle

Kozlowski, David J ; Whitfield, Tanya T. ; Hukriede, Neil A. ; Lam, Wai K. ; Weinberg, Eric S. / The zebrafish dog-eared mutation disrupts eya1, a gene required for cell survival and differentiation in the inner ear and lateral line. In: Developmental Biology. 2005 ; Vol. 277, No. 1. pp. 27-41.
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