Zinc-finger transcription factors and the response of non-myelinating Schwann cells to axonal injury

Abstract

Schwann cell (SCs) are the glia of the peripheral nervous system. During development, a common precursor develops into two distinct types of SCs: myelinating SCs and non-myelinating SCs. There is little literature regarding the non-myelinating variety of SCs, specifically a type of non-myelinating SC found at the neuromuscular junction (NMJ), the terminal Schwann cell (tSC). Terminal SCs are critical for the maintenance and recovery of the NMJ. Peripheral nerve injury causes tSCs to become reactive, a state characterized by changes in gene expression and the extension of cellular processes. It is in this state, that tSCs help to restore functionality to the denervated junction. What drives tSCs to become reactive after injury remains largely unknown. Previously, nine zinc-finger proteins (ZFPs), a class of transcription factors, have been implicated in SC development and differentiation. As a result, transcription factors from the ZFP family were considered as potential candidates that may drive the activation of tSCs. Because tSCs are few and far between, only two-six cells cover the NMJ, I used a largely non-myelinated nerve of the autonomic system, the cervical sympathetic trunk (CST), to search for ZFP candidates. I created a cDNA library from both control and denervated CST resulting in 40 unique ZFPs. Six of these genes were studied futher: Zipro1, Zfp36, Zfp612, Zfp180, Zfp111 and Zfp629. I found a near two-fold increase in Zipro1 mRNA and protein in denervated CST, and no change in the other five ZFPs (results from Zfp629 remain inconclusive). Using an antibody against Zipro1, I located this increase of Zipro1 to the SCs of the denervated CST. I also found Zipro1 expression in tSCs and an increase of 19% in tSCs of denervated rat muscle. Upregulation of Zipro1 in non-myelinating SCs suggests that Zipro1 may have a role in the activation of tSCs. Further study is needed in order to clarify the extent of Zipro1's involvement.