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

42 Citations (Scopus)

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 2004

Fingerprint

Deafness
Zebrafish
Hyaluronic Acid
Ear
Hearing Loss
Cartilage
Semicircular Canals
Genes
Uridine Diphosphate Glucose Dehydrogenase
Branchial Region
Reverse Genetics
Morpholinos
Recycling
Extracellular Matrix
Proteins
Nucleotides
Phenotype
Enzymes
Autosomal Dominant 5 Deafness

Keywords

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

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

The deafness gene dfna5 is crucial for ugdh expression and HA production in the developing ear in zebrafish. / Busch-Nentwich, Elisabeth; Söllner, Christian; Roehl, Henry; Nicolson, Teresa.

In: Development, Vol. 131, No. 4, 02.2004, p. 943-951.

Research output: Contribution to journalArticle

Busch-Nentwich, Elisabeth ; Söllner, Christian ; Roehl, Henry ; Nicolson, Teresa. / The deafness gene dfna5 is crucial for ugdh expression and HA production in the developing ear in zebrafish. In: Development. 2004 ; Vol. 131, No. 4. pp. 943-951.
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