Glial growth factor 2, a soluble neuregulin, directly increases Schwann cell motility and indirectly promotes neurite outgrowth

Abstract

Schwann cells proliferate, migrate, and act as sources of neurotrophic support during development and regeneration of peripheral nerves. Recent studies have demonstrated that neuregulins, a family of growth factors secreted by developing motor and peripheral neurons, influence Schwann cell development. In this study, we use three distinct assays to show that glial growth factor 2 (GGF2), a secreted neuregulin, exerts multiple effects on mature Schwann cells in vitro. At doses submaximal for proliferation, GGF2 increases the motility of Schwann cells cultured on peripheral nerve cryosections. Furthermore, in a novel bioassay, focal application of GGF2 causes directed migration in conventional monolayer cultures of Schwann cells. At higher doses, GGF2 causes proliferation, as described previously. In a new explant culture system designed to emulate entubulation repair of transected peripheral nerves, GGF2 concentrations greater than necessary to saturate the mitotic response induce the secretion by Schwann cells of activities that promote sympathetic neuron survival and outgrowth. These findings support a model in which neuregulins secreted by peripheral neurons are key components of reciprocal neuron-glia interactions that are important for peripheral nerve development and regeneration.