Dual regulation of GAP-43 gene expression by nerve growth factor and glucocorticoids

GAP-43 is a neural-specific protein that is believed integral to neurite growth and to the plasticity of neuronal structure. Its gene expression is regulated in vivo and correlates with periods of axonal growth. We investigated the regulation of GAP-43 gene expression in PC12 cells, which are believed to resemble precursor cells of the adrenomedullary lineage. In these cells, nerve growth factor (NGF) increases GAP-43 expression, and corticosteroids decrease it. Corticosteroids diminish GAP-43 levels even in cells already differentiated by NGF, as well as in primary neurons of the superior cervical ganglion. Neither the NGF nor the steroid effect requires new protein synthesis. Nuclear run-on experiments show that the steroid repression is mediated at the level of gene transcription but that the NGF effect is likely to be posttranscriptional. NGF and corticosteroids are known to regulate bimodally the cell fate decision of sympathoadrenal precursors, with NGF promoting the neuronal phenotype and steroids promoting the chromaffin phenotype. The regulation of GAP-43 is consistent with the notion that this gene is bimodally regulated during these cell fate decisions.