Differential activation of NGF receptor and early response genes in neural crest-derived cells.

Nerve growth factor (NGF) binds to a specific cell surface receptor (NGFR) that exists in high affinity (now called trk) and low affinity (now called p75NGFR) forms. NGF-responsive neurons express both forms of the receptor, while Schwann cells, during early development and after nerve injury, express only low affinity p75NGFR. In an attempt to determine whether NGF alters patterns of gene expression in p75NGFR-bearing Schwann cells, we examined the regulation of three early response genes (NGFI-A, NGFI-B, and c-fos) in JS1 rat schwannoma cells. Although these genes are markedly activated by NGF in PC12 (rat pheochromocytoma) cells, NGF has no effect on their transcription in JS1 cells. In contrast to PC12 cells, NGFI-A and NGFI-B are constitutively expressed in JS1 cells, whereas the c-fos gene is not expressed. Treating JS1 cells with cycloheximide (CHX), an inhibitor of protein synthesis that commonly potentiates induction of early response genes by presumably inhibiting synthesis of transcriptional repressors, markedly induces the transcription of NGFI-A and c-fos as well as p75NGFR genes. These data suggest that transcriptional repression plays a major role in the regulation of these genes and that the markedly different regulation of NGFI-A, NGFI-B, and c-fos, all of which encode transcriptional regulators, may be important in guiding the differentiation of these cell types.