Abstract
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.