In Search of a Terminal Schwann Cell-Specific Marker: Does a Tool Exist?
Alison Snyder-Warwick, MD, Katherine Santosa, MD, Albina Jablonka-Shariff, PhD.
Washington University School of Medicine, St Louis, MO, USA.
Purpose: Specialized structures at the neuromuscular junction (NMJ) facilitate the interface between nerve and muscle. Terminal Schwann cells (tSCs) are glial cells present at the NMJ. While these non-myelinating Schwann cells have been implicated in multiple functional roles, there is no known marker specific to tSCs, making isolation and investigation of this cell type challenging. We sought to identify genetic markers unique to tSCs.
Methods: A novel component dissection technique was utilized to isolate the tSC-containing endplate band from the sternomastoid muscles of young adult S100-GFP mice. RNA was isolated from samples containing: 1) Endplate bands (tSCs + nerve + muscle), 2) Nerve, and 3) Muscle and prepared for microarray analysis. Rank-order analysis was performed to identify genes specific to tSCs.
Results: Preliminary data have generated a total of 11 genes unique to the NMJ. Our short list of candidate genes specific to tSCs includes D-2-hydroxyglutarate dehydrogenase (D2hgdh), Collagen Q (ColQ), and T-bet 21 (Tbx21). These genes were upregulated at the NMJ by 4- to 11-fold compared to muscle or nerve parts alone (p<0.05). D2hgdh protein expression co-localizes with tSCs and is not noted in myelinating SCs from sciatic nerve. Current validation studies of these candidate genes are ongoing.
Conclusions: Given their unique functional roles, tSCs likely have a unique transcriptome that differentiate them from other Schwann cell types. Identification of genetic specificity for tSCs facilitates improved methods to investigate these unique cells and ultimately allows for transgenic mouse line creation that permits Cre-mediated recombination in tSCs.
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