The deafness gene dfna5 is crucial for ugdh expression and HA production in the developing ear in zebrafish

Elisabeth Busch-Nentwich, Christian Söllner, Henry Roehl, Teresa Nicolson

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

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 reverse-genetic 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.

Original languageEnglish (US)
Pages (from-to)943-951
Number of pages9
JournalDevelopment
Volume131
Issue number4
DOIs
StatePublished - Feb 1 2004

Keywords

  • Deafness
  • Hyaluronic acid
  • Pharyngeal cartilage
  • Semicircular canals
  • UDP-glucose dehydrogenase
  • Zebrafish
  • dfna5

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Fingerprint Dive into the research topics of 'The deafness gene dfna5 is crucial for ugdh expression and HA production in the developing ear in zebrafish'. Together they form a unique fingerprint.

  • Cite this