Molecular mechanisms underlying inner ear patterning defects in kreisler mutants

Dev Biol. 2006 Jan 15;289(2):308-17. doi: 10.1016/j.ydbio.2005.10.007. Epub 2005 Dec 1.


Prior studies have shown that kreisler mutants display early inner ear defects that are related to abnormal hindbrain development and signaling. These defects in kreisler mice have been linked to mutation of the kr/mafB gene. To investigate potential relevance of kr/mafB and abnormal hindbrain development in inner ear patterning, we analyzed the ear morphogenesis in kreisler mice using a paint-fill technique. We also examined the expression patterns of a battery of genes important for normal inner ear patterning and development. Our results indicate that the loss of dorsal otic structures such as the endolymphatic duct and sac is attributable to the downregulation of Gbx2, Dlx5 and Wnt2b in the dorsal region of the otocyst. In contrast, the expanded expression domain of Otx2 in the ventral otic region likely contributes to the cochlear phenotype seen in kreisler mutants. Sensory organ development is also markedly disrupted in kreisler mutants. This pattern of defects and gene expression changes is remarkably similar to that observed in Gbx2 mutants. Taken together, the data show an important role for hindbrain cues, and indirectly, kr/mafB, in guiding inner ear morphogenesis. The data also identify Gbx2, Dlx5, Wnt2b and Otx2 as key otic genes ultimately affected by perturbation of the kr/mafB-hindbrain pathway.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Body Patterning / genetics*
  • Body Patterning / physiology
  • Cell Death / genetics
  • Cell Death / physiology
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Cell Proliferation
  • Cochlea / embryology
  • Cochlea / metabolism
  • Ear, Inner / embryology*
  • Ear, Inner / metabolism*
  • Endolymphatic Duct / cytology
  • Endolymphatic Duct / metabolism
  • Gene Expression Regulation, Developmental*
  • Glycoproteins / metabolism
  • Homeodomain Proteins / metabolism
  • In Situ Hybridization
  • MafB Transcription Factor / genetics*
  • MafB Transcription Factor / metabolism
  • Mice
  • Mice, Inbred C3H
  • Morphogenesis / genetics
  • Mutation
  • Oncogene Proteins / genetics*
  • Oncogene Proteins / metabolism
  • Otx Transcription Factors / metabolism
  • Rhombencephalon / embryology
  • Rhombencephalon / metabolism
  • Semicircular Canals / embryology
  • Semicircular Canals / metabolism
  • Signal Transduction / genetics
  • Wnt Proteins / metabolism


  • Biomarkers
  • Dlx5 protein, mouse
  • Gbx2 protein, mouse
  • Glycoproteins
  • Homeodomain Proteins
  • MafB Transcription Factor
  • Mafb protein, mouse
  • Oncogene Proteins
  • Otx Transcription Factors
  • Otx2 protein, mouse
  • Wnt Proteins
  • Wnt2b protein, mouse