Schwann cell apoptosis at developing neuromuscular junctions is regulated by glial growth factor

Denervated adult mammalian muscle fibres are reinnervated by regenerating axons and, in the case of partially denervated muscles, by sprouts extended from remaining, intact axons. Recent experiments suggest that Schwann cells (SCs) regulate these events, inducing and guiding axonal outgrowth through the processes they extend. In contrast to adults, reinnervation o denervated neonatal muscles is deficient and axonal sprouting is absent. In light of the proposed roles for SCs in these processes, we examined whether SCs in neonatal muscles exhibit altered responses to denervation. We report here that neonatal denervation leads to the rapid, apoptotic death of SCs at rat neuro-muscular junctions. Injection of glial growth factor, a member of the neuregulin family of trophic factors present in developing sensory and motor neurons, prevents this apoptosis in vivo. These results provide further evidence for the importance of SCs in regulating nerve growth and suggest that axon-Schwann cell trophic interactions play a role in the normal development of the neuromuscular system.