The zebrafish dog-eared mutation disrupts eya1, a gene required for cell survival and differentiation in the inner ear and lateral line.
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.
Kozlowski
David J
DJ
Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Whitfield
Tanya T
TT
Hukriede
Neil A
NA
Lam
Wai K
WK
Weinberg
Eric S
ES
D000818:Animals; D017209:Apoptosis; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D002874:Chromosome Mapping; D007758:Ear, Inner / Q000196:embryology*; D018069:Hair Cells, Vestibular / Q000196:embryology; D047908:Intracellular Signaling Peptides and Proteins; D009154:Mutation; D009687:Nuclear Proteins; D017027:Protein Tyrosine Phosphatases; D012333:RNA, Messenger / Q000032:analysis; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D015027:Zebrafish; D029961:Zebrafish Proteins
C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D029961:Zebrafish Proteins; C525813:bmp4 protein, zebrafish; D017027:Protein Tyrosine Phosphatases; C501158:eya1 protein, zebrafish