EXPRESSION OF THE NEU PROTOONCOGENE BY SCHWANN-CELLS DURING PERIPHERAL-NERVE DEVELOPMENT AND WALLERIAN DEGENERATION

The neu gene, which encodes a putative tyrosine kinase growth factor receptor termed p185neu, was originally identified as a dominant transforming gene in neurogliomas and schwannomas induced by transplacental treatment of rat embryos with ethylnitrosourea. The present studies were undertaken to determine the expression pattern of the neu gene in peripheral nerve. Northern blot analysis of total RNA isolated from rat sciatic nerves demonstrated prominent neu mRNA expression on postnatal days 1 and 7, with substantially lower expression up to adulthood. Immunohistochemical studies confirmed expression of p185neu by Schwann cells (SC) in developing sciatic nerve and minimal p185neu immunoreactivity in adult nerves. However, neu mRNA and p185neu protein progressively increased following sciatic nerve transection in adult animals. In addition, neu mRNA and p185neu were found in neonatal rat sciatic nerve SC and several SC-derived cell lines. In resting SC, neu mRNA was expressed at a low level, but was greatly increased by treatment with forskolin and glial growth factor. These studies demonstrate that the neu gene and its protein product, p185neu, are expressed by SC both in vivo and in vitro and suggest that p185neu plays a role in the regulation of SC proliferation or differentiation.