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          Institute: MPI für Entwicklungsbiologie     Collection: Abteilungsunabhängige Arbeitsgruppen     Display Documents



ID: 176169.0, MPI für Entwicklungsbiologie / Abteilungsunabhängige Arbeitsgruppen
The deafness gene dfna5 is crucial for ugdh expression and HA production in the developing ear in zebrafish
Authors:Busch-Nentwich, Elisabeth; Söllner, Christian; Roehl, Henry; Nicolson, Theresa
Language:English
Date of Publication (YYYY-MM-DD):2004-02
Title of Journal:Development
Volume:131
Issue / Number:4
Start Page:943
End Page:951
Sequence Number of Article:14736743
Review Status:not specified
Audience:Not Specified
Abstract / Description:Over 30 genes responsible for human hereditary hearing loss have been identified during the last 10 years. The proteins encoded by these genes play roles in a diverse set of cellular functions ranging from transcriptional regulation to K(+) recycling. In a few cases, the genes are novel and do not give much insight into the cellular or molecular cause for the hearing loss. Among these poorly understood deafness genes is DFNA5. How the truncation of the encoded protein DFNA5 leads to an autosomal dominant form of hearing loss is not clear. In order to understand the biological role of Dfna5, we took a reversegenetic approach in zebrafish. Here we show that morpholino antisense nucleotide knock-down of dfna5 function in zebrafish leads to disorganization of the developing semicircular canals and reduction of pharyngeal cartilage. This phenotype closely resembles previously isolated zebrafish craniofacial mutants including the mutant jekyll. jekyll encodes Ugdh [uridine 5'-diphosphate (UDP)-glucose dehydrogenase], an enzyme that is crucial for production of the extracellular matrix component hyaluronic acid (HA). In dfna5 morphants, expression of ugdh is absent in the developing ear and pharyngeal arches, and HA levels are strongly reduced in the outgrowing protrusions of the developing semicircular canals. Previous studies suggest that HA is essential for differentiating cartilage and directed outgrowth of the epithelial protrusions in the developing ear. We hypothesize that the reduction of HA production leads to uncoordinated outgrowth of the canal columns and impaired facial cartilage differentiation.
External Publication Status:published
Document Type:Article
Affiliations:MPI für Entwicklungsbiologie/Abteilungsunabhängige Arbeitsgruppen
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