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

Published

Journal Article

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.

Full Text

Cited Authors

  • Nadeau, S; Hein, P; Fernandes, KJL; Peterson, AC; Miller, FD

Published Date

  • August 2005

Published In

Volume / Issue

  • 29 / 4

Start / End Page

  • 525 - 535

PubMed ID

  • 15936952

Pubmed Central ID

  • 15936952

Electronic International Standard Serial Number (EISSN)

  • 1095-9327

International Standard Serial Number (ISSN)

  • 1044-7431

Digital Object Identifier (DOI)

  • 10.1016/j.mcn.2005.04.004

Language

  • eng