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

The molecular mechanisms responsible for inducing gene expression following neuronal injury are not well understood. Here, we address this issue by focusing upon C/EBPβ, a transcription factor implicated in cellular injury and regeneration. We show that C/EBPβ mRNA is expressed in neurons throughout the mature brain and that levels of both C/EBPβ mRNA and phosphoprotein are increased in facial motor neurons following axonal injury. To determine the importance of these increases, we examined the regeneration-associated Tα1 α-tubulin gene which contains functional C/EBP binding sites in its promoter. In transgenic mice, expression of a minimal 176 nucleotide Tα1 α-tubulin promoter:nlacZ reporter gene was upregulated in injured facial motor neurons. This injury-induced transcriptional increase was inhibited in C/EBPβ −/− mice. A similar inhibition was observed in C/EBPβ −/− mice that carried a larger 1.1-kb promoter Tα1:nlacZ reporter construct. Moreover, in situ hybridization revealed that the injury-induced upregulation of the endogenous mouse α1 α-tubulin mRNA, and of a second regeneration-associated mRNA, GAP-43, was inhibited in C/EBPβ −/− mice. Thus, C/EBPβ is essential for the neuronal injury response, acting to transcriptionally activate regeneration-associated gene expression.