Human ESC-derived neural crest model reveals a key role for SOX2 in sensory neurogenesis

Cell Stem Cell. 2011 May 6;8(5):538-51. doi: 10.1016/j.stem.2011.03.011.

Abstract

The transcription factor SOX2 is widely known to play a critical role in the central nervous system; however, its role in peripheral neurogenesis remains poorly understood. We recently developed an hESC-based model in which migratory cells undergo epithelial to mesenchymal transition (EMT) to acquire properties of neural crest (NC) cells. In this model, we found that migratory NC progenitors downregulate SOX2, but then start re-expressing SOX2 as they differentiate to form neurogenic dorsal root ganglion (DRG)-like clusters. SOX2 downregulation was sufficient to induce EMT and resulted in massive apoptosis when neuronal differentiation was induced. In vivo, downregulation of SOX2 in chick and mouse NC cells significantly reduced the numbers of neurons within DRG. We found that SOX2 binds directly to NGN1 and MASH1 promoters and is required for their expression. Our data suggest that SOX2 plays a key role for NGN1-dependent acquisition of neuronal fates in sensory ganglia.

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
  • Cell Count
  • Cell Movement
  • Chickens
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism*
  • Epithelial-Mesenchymal Transition
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / metabolism*
  • Gene Expression Regulation, Developmental
  • Humans
  • Mice
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neural Crest / cytology
  • Neurogenesis* / genetics
  • Organ Specificity
  • Protein Binding
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism*
  • Sensory Receptor Cells / cytology*

Substances

  • ASCL1 protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • NEUROG1 protein, human
  • Nerve Tissue Proteins
  • SOX2 protein, human
  • SOXB1 Transcription Factors