Expression and function of scleraxis in the developing auditory system

PLoS One. 2013 Sep 13;8(9):e75521. doi: 10.1371/journal.pone.0075521. eCollection 2013.

Abstract

A study of genes expressed in the developing inner ear identified the bHLH transcription factor Scleraxis (Scx) in the developing cochlea. Previous work has demonstrated an essential role for Scx in the differentiation and development of tendons, ligaments and cells of chondrogenic lineage. Expression in the cochlea has been shown previously, however the functional role for Scx in the cochlea is unknown. Using a Scx-GFP reporter mouse line we examined the spatial and temporal patterns of Scx expression in the developing cochlea between embryonic day 13.5 and postnatal day 25. Embryonically, Scx is expressed broadly throughout the cochlear duct and surrounding mesenchyme and at postnatal ages becomes restricted to the inner hair cells and the interdental cells of the spiral limbus. Deletion of Scx results in hearing impairment indicated by elevated auditory brainstem response (ABR) thresholds and diminished distortion product otoacoustic emission (DPOAE) amplitudes, across a range of frequencies. No changes in either gross cochlear morphology or expression of the Scx target genes Col2A, Bmp4 or Sox9 were observed in Scx(-/-) mutants, suggesting that the auditory defects observed in these animals may be a result of unidentified Scx-dependent processes within the cochlea.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / biosynthesis*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Bone Morphogenetic Protein 4 / biosynthesis
  • Bone Morphogenetic Protein 4 / genetics
  • Cochlear Duct / cytology
  • Cochlear Duct / embryology*
  • Collagen Type II / biosynthesis
  • Collagen Type II / genetics
  • Gene Expression Regulation, Developmental / physiology*
  • Hair Cells, Auditory, Inner / cytology
  • Hair Cells, Auditory, Inner / metabolism*
  • Mice
  • Mice, Knockout
  • Organogenesis / physiology*
  • SOX9 Transcription Factor / biosynthesis
  • SOX9 Transcription Factor / genetics

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Bmp4 protein, mouse
  • Bone Morphogenetic Protein 4
  • Col2a1 protein, mouse
  • Collagen Type II
  • SOX9 Transcription Factor
  • Scx protein, mouse
  • Sox9 protein, mouse