A transcriptional role for C/EBP beta in the neuronal response to axonal injury

Mol Cell Neurosci. 2005 Aug;29(4):525-35. doi: 10.1016/j.mcn.2005.04.004.

Abstract

The molecular mechanisms responsible for inducing gene expression following neuronal injury are not well understood. Here, we address this issue by focusing upon C/EBPbeta, a transcription factor implicated in cellular injury and regeneration. We show that C/EBPbeta mRNA is expressed in neurons throughout the mature brain and that levels of both C/EBPbeta mRNA and phosphoprotein are increased in facial motor neurons following axonal injury. To determine the importance of these increases, we examined the regeneration-associated Talpha1 alpha-tubulin gene which contains functional C/EBP binding sites in its promoter. In transgenic mice, expression of a minimal 176 nucleotide Talpha1 alpha-tubulin promoter:nlacZ reporter gene was upregulated in injured facial motor neurons. This injury-induced transcriptional increase was inhibited in C/EBPbeta -/- mice. A similar inhibition was observed in C/EBPbeta -/- mice that carried a larger 1.1-kb promoter Talpha1:nlacZ reporter construct. Moreover, in situ hybridization revealed that the injury-induced upregulation of the endogenous mouse alpha1 alpha-tubulin mRNA, and of a second regeneration-associated mRNA, GAP-43, was inhibited in C/EBPbeta -/- mice. Thus, C/EBPbeta is essential for the neuronal injury response, acting to transcriptionally activate regeneration-associated gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism*
  • Binding Sites / genetics
  • CCAAT-Enhancer-Binding Protein-beta / genetics*
  • CCAAT-Enhancer-Binding Protein-beta / metabolism
  • Facial Nerve Injuries / metabolism*
  • Facial Nerve Injuries / physiopathology
  • Female
  • GAP-43 Protein / genetics
  • Gene Expression Regulation / genetics
  • Genes, Reporter / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Neurons / metabolism*
  • Nerve Regeneration / genetics*
  • Phosphoproteins / genetics
  • Promoter Regions, Genetic / genetics
  • RNA, Messenger / metabolism
  • Regulatory Elements, Transcriptional / genetics
  • Retrograde Degeneration / metabolism*
  • Retrograde Degeneration / physiopathology
  • Transcriptional Activation / genetics
  • Tubulin / genetics
  • Up-Regulation / genetics

Substances

  • CCAAT-Enhancer-Binding Protein-beta
  • GAP-43 Protein
  • Phosphoproteins
  • RNA, Messenger
  • Tubulin