Sox2 regulation of hair cell development: incoherence makes sense

Hear Res. 2013 Mar;297:20-9. doi: 10.1016/j.heares.2012.11.003. Epub 2012 Nov 12.

Abstract

The function of the inner ear relies on different specialized cell types: hair cells, supporting cells and otic neurons. During development, these cell types are generated from the neurosensory domain of the otic placode with a stereotyped spatial and temporal pattern. We discuss here the role played by Sox2 in the establishment of the neurosensory competence at early stages of inner ear development, and how this resolves in the sequential generation of neurons and hair cells. Sox2 is expressed in the neurosensory domain of the otic placode and it is necessary and sufficient for hair cell development. The prosensory function of Sox2 relies on its ability to directly bind Atoh1 regulatory regions and activate its expression. This function is likely mediated through the interaction with partner factors, some of which are just starting to be disclosed. However, the regulation of proneural genes by Sox2 is seemingly contradictory, because it also inhibits the function of Atoh1 and hence the differentiation of hair cells. This is because Sox2 triggers an incoherent feed forward loop by which in parallel to the activation of Atoh1, Sox2 also induces inhibitory factors that counteract its function. As a result, neurosensory competence is established in the early otic placode but hair cell differentiation procrastinated. More generally, this suggests that cell diversification may arise from the selective de-repression of an initial multicompetent state.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Differentiation
  • Cell Lineage
  • Ear, Inner / embryology*
  • Ear, Inner / metabolism
  • Gene Expression Regulation, Developmental*
  • Hair Cells, Auditory / cytology*
  • Humans
  • Mice
  • Microscopy, Fluorescence / methods
  • Neurons / metabolism
  • Protein Binding
  • SOXB1 Transcription Factors / metabolism*
  • Signal Transduction

Substances

  • Atoh1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • SOXB1 Transcription Factors