Zinc-finger Transcription Factors and the Response of Non-myelinating Schwann Cells to Axonal Injury

Terminal Schwann cells (tSCs) are non-myelinating glia that cover 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. Terminal SCs 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 SC development and myelination, and levels of one such protein were reported increased in other nonmyelinating 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 RT-PCR. 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 Zipro 1 is expressed in tSCs and its levels increased following skeletal muscle denervation. Thus, Zipro1 is a