Role of Oncogenes in Neural Regeneration
In the intact rat sciatic nerve the nonneuronal cells surrounding the axons synthesize very low amounts of nerve growth factor (NGF). After cutting the nerve there is a biphasic increase in levels of NGF-mRNA in the distal nerve segment and in the tip of the proximal stump where axonal regrowth is initiated. The rapid transient increase of NGF-mRNA (first phase) is preceded by an almost immediate elevation in the levels of the mRNAs coding for the nuclear protooncogenes c-fos and c-jun. A trans-activating effect of FOS on the NGF-promoter was demonstrated by using sciatic nerve derived fibroblasts carrying an exogenous inducible fos gene. Further analysis shows that an AP-1 consensus sequence located in the first intron of the NGF gene is essential for the fos-mediated increase of NGF-mRNA levels.