Atoh1 directs hair cell differentiation and survival in the late embryonic mouse inner ear

Dev Biol. 2013 Sep 15;381(2):401-10. doi: 10.1016/j.ydbio.2013.06.022. Epub 2013 Jun 21.


Atoh1 function is required for the earliest stages of inner ear hair cell development, which begins during the second week of gestation. Atoh1 expression in developing hair cells continues until early postnatal ages, but the function of this late expression is unknown. To test the role of continued Atoh1 expression in hair cell maturation we conditionally deleted the gene in the inner ear at various embryonic and postnatal ages. In the organ of Corti, deletion of Atoh1 at E15.5 led to the death of all hair cells. In contrast, deletion at E16.5 caused death only in apical regions, but abnormalities of stereocilia formation were present throughout the cochlea. In the utricle, deletion at E14.5 or E16.5 did not cause cell death but led to decreased expression of myosin VIIa and failure of stereocilia formation. Furthermore, we show that maintained expression of Barhl1 and Gfi1, two transcription factors implicated in cochlear hair cell survival, depends upon continued Atoh1 expression. However, maintained expression of Pou4f3 and several hair cell-specific markers is independent of Atoh1 expression. These data reveal novel late roles for Atoh1 that are separable from its initial role in hair cell development.

Keywords: Cochlea; Development; Differentiation; Hearing; Vestibular system.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Biomarkers / metabolism
  • Cell Death
  • Cell Differentiation*
  • Cell Survival
  • Cochlea / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Embryo, Mammalian / metabolism
  • Female
  • Gene Deletion
  • Gene Expression Regulation, Developmental*
  • Hair Cells, Auditory / drug effects
  • Hair Cells, Auditory / metabolism
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Pregnancy
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Saccule and Utricle / cytology*
  • Saccule and Utricle / embryology
  • Saccule and Utricle / metabolism
  • Stereocilia / metabolism
  • Tamoxifen
  • Transcription Factor Brn-3C / genetics
  • Transcription Factor Brn-3C / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Atoh1 protein, mouse
  • Barhl1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers
  • DNA-Binding Proteins
  • Gfi1 protein, mouse
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Pou4f3 protein, mouse
  • Repressor Proteins
  • Transcription Factor Brn-3C
  • Transcription Factors
  • Tamoxifen