Lineage tracing of Sox2-expressing progenitor cells in the mouse inner ear reveals a broad contribution to non-sensory tissues and insights into the origin of the organ of Corti

Dev Biol. 2016 Jun 1;414(1):72-84. doi: 10.1016/j.ydbio.2016.03.027. Epub 2016 Apr 14.

Abstract

The transcription factor Sox2 is both necessary and sufficient for the generation of sensory regions of the inner ear. It regulates expression of the Notch ligand Jag1 in prosensory progenitors, which signal to neighboring cells to up-regulate Sox2 and sustain prosensory identity. However, the expression pattern of Sox2 in the early inner ear is very broad, suggesting that Sox2-expressing progenitors form a wide variety of cell types in addition to generating the sensory regions of the ear. We used Sox2-CreER mice to follow the fates of Sox2-expressing cells at different stages in ear development. We find that Sox2-expressing cells in the early otocyst give rise to large numbers of non-sensory structures throughout the inner ear, and that Sox2 only becomes a truly prosensory marker at embryonic day (E)11.5. Our fate map reveals the organ of Corti derives from a central domain on the medial side of the otocyst and shows that a significant amount of the organ of Corti derives from a Sox2-negative population in this region.

Keywords: Cochlea; Inner ear; Organ of Corti; Otocyst; Sensory; Sox2.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Differentiation / analysis
  • Cell Lineage
  • Ear, Inner / cytology*
  • Ear, Inner / embryology
  • Gene Expression Regulation, Developmental
  • Gene Knock-In Techniques
  • Genes, Reporter
  • Imaging, Three-Dimensional
  • Jagged-1 Protein / biosynthesis
  • Jagged-1 Protein / genetics
  • Luminescent Proteins / analysis
  • Mice
  • Mice, Transgenic
  • Neural Stem Cells / cytology*
  • Organ of Corti / cytology
  • Organ of Corti / embryology*
  • Receptors, Notch / physiology
  • SOXB1 Transcription Factors / analysis*
  • Signal Transduction / physiology

Substances

  • Antigens, Differentiation
  • Jag1 protein, mouse
  • Jagged-1 Protein
  • Luminescent Proteins
  • Receptors, Notch
  • SOXB1 Transcription Factors