Signal involved in the switch to fate commitment of bone marrow-derived Schwann cells

Abstract

Schwann cell transplantation can promote axonal regrowth and remyelination following nerve injury. Our group has reported the generation of fate-committed bone marrow-derived Schwann cells by co-culturing with dorsal root ganglia (DRG, E14/15 rats) neurons (Shea et. al, 2010). Juxtacrine/paracrine signals from DRG neurons are therefore thought to provide instructive cues to direct the switch of bone marrow-derived Schwann cell-like cells (SCLC) to fate committed Schwann cells. We hypothesized that neuregulin 1 Type III (Nrg 1 Type III), the membrane bound form of Nrg contributes to the switch but not the soluble isoforms. SCLC treated with soluble Nrg did not show significant changes in morphology nor marker expression when compared with untreated SCLCs. Purified DRG neurons were found to express Nrg 1 Type III as indicated by immunocytochemistry and polymerase chain reaction for the mRNA. A Nrg 1 Type III construct was also made for transfection into HEK 293T and mouse embryonic fibroblasts (MEF) such that these could be tested as surrogate cell types in co-culture with SCLCs to pursue cell-specific effects of Nrg 1 Type III on differentiation of SCLCs. The findings promise a way for generating fate committed Schwann cells for autologous transplantation into nerve lesion sites to promote functional recovery.