title: A transcriptional role for C/EBP beta in the neuronal response to axonal injury.
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.
authors.affiliation: Developmental Biology and Neurobiology and Behavior, Hospital for Sick Children, 3203 Black Wing, Toronto, Ontario, Canada M5G 1X5.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Nadeau
authors.forename: Paul
authors.initials: P
authors.lastname: Hein
authors.forename: Karl J L
authors.initials: KJ
authors.lastname: Fernandes
authors.forename: Alan C
authors.initials: AC
authors.lastname: Peterson
authors.forename: Freda D
authors.initials: FD
authors.lastname: Miller
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics* / Q000378:metabolism; D020220:Facial Nerve Injuries / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D019922:GAP-43 Protein / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009046:Motor Neurons / Q000378:metabolism*; D009416:Nerve Regeneration / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional / Q000235:genetics; D012183:Retrograde Degeneration / Q000378:metabolism* / Q000503:physiopathology; D015533:Transcriptional Activation / Q000235:genetics; D014404:Tubulin / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D019922:GAP-43 Protein; D010750:Phosphoproteins; D012333:RNA, Messenger; D014404:Tubulin