Induction of zinc-finger proliferation 1 expression in non-myelinating Schwann cells after denervation

Terminal Schwann cells (tSCs) are non-myelinating glia that wrap the nerve terminal at the neuromuscular junction. They are required for the maintenance of the neuromuscular synapse and are likely to play essential roles in the restoration of synaptic connections after nerve injury. tSCs acquire a reactive phenotype after nerve damage characterized by the extension of cellular processes that may facilitate reinnervation. The molecular signaling events underpinning the tSC reactive state remain elusive, in particular, little is known about transcription factors involved in the transcriptional reprogramming during tSC activation. Prior research implicated nine members of the zinc-finger transcription factor family in Schwann cell (SC) development and myelination, and levels of one such protein were reported increased in other non-myelinating SCs after denervation. We hypothesize that zinc-finger transcription factors could play a role during tSC activation. Because of their relative paucity, tSCs are difficult to study molecularly. Here, we used the rat cervical sympathetic trunk (CST), an autonomic nerve in which non-myelinating SCs are the predominant cell type, to isolate zinc-finger protein (ZFP) cDNAs by reverse transcriptase-polymerase chain reaction. We isolated 29 unique ZFP sequences of which zinc proliferation 1 (Zipro1) was the most abundant. We found that after CST transection, levels for Zipro1 mRNA doubled and that Zipro1 protein expression increased in non-myelinating CST SCs. We also determined that Zipro1 is expressed in tSCs and its levels increased following skeletal muscle denervation. Thus, Zipro1 is a good candidate for a transcription factor involved in activation of non-myelinating SCs in general, and tSCs in particular.