CtBPs sense microenvironmental oxygen levels to regulate neural stem cell state

Cell Rep. 2014 Aug 7;8(3):665-70. doi: 10.1016/j.celrep.2014.06.057. Epub 2014 Jul 31.


Bone morphogenetic proteins (BMPs) secreted by the dorsal neural tube and overlying ectoderm are key signals for the specification of the roof plate and dorsal interneuron populations. However, the signals that confer nonneurogenic character to the roof plate region are largely unknown. We report that the roof plate region shows elevated oxygen levels compared to neurogenic regions of the neural tube. These high oxygen levels are required for the expression of the antineuronal transcription factor Hes1 in the roof plate region. The transcriptional corepressor CtBP is a critical mediator of the oxygen-sensing response. High oxygen promotes a decrease in the CtBP occupancy of the promoter of Hes1. Furthermore, under conditions of high oxygen and BMP, CtBP associates with HES1 and represses neurogenesis. We propose that CtBP integrates signals originating from microenvironmental levels of oxygen and BMP to confer nonneurogenic character to the roof plate region.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Hypoxia
  • Cells, Cultured
  • Chick Embryo
  • Eye Proteins / genetics
  • Eye Proteins / metabolism*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism*
  • Neural Tube / cytology
  • Neural Tube / metabolism
  • Neurogenesis*
  • Oxygen / metabolism*
  • Promoter Regions, Genetic
  • Rats
  • Stem Cell Niche*
  • Transcription Factor HES-1
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Basic Helix-Loop-Helix Transcription Factors
  • Carrier Proteins
  • Ctbp1 protein, rat
  • Ctbp2 protein, rat
  • Eye Proteins
  • Hes1 protein, rat
  • Homeodomain Proteins
  • Transcription Factor HES-1
  • Transcription Factors
  • Oxygen