Preservation of Schwann cell identity in vitro through bone morphogenetic protein signaling

Abstract

In the injured nerve environment, Schwann cells switch on an axon-supportive program that improves nerve regeneration and functional recovery. We therefore devised a protocol to derive Schwann cells from bone marrow stromal cells (Shea et al, Exp Neurol, 2010). In standard cultures of Schwann cells extracted from sciatic nerves of neonatal rats, we serendipitously observed expression of Olig2, the obligate transcription factor for oligodendrogenesis, as of 25 DIV; these Olig2-positive cells showed polydendrocytic morphology reminiscent of oligodendrocyte precursors. Increase in Olig2-positive cells was accompanied by decline in p75-immunopositivity among continuing cultures of the Schwann cells. We then hypothesized that the peripheral nerve environment harbours factors that preserve Schwann cell identity. In support of this, co-cultures of 25-DIV Schwann cells with neurons purified from dorsal root ganglia (DRG, E15) led to decline in incidence of Olig2-positive oligodendrocyte precursor cells. Our search for factors that suppress Olig2 expression found BMP4-immunoreactivity localized to the DRG neurons. Supplementation of BMP4 to 25-DIV Schwann cell cultures suppressed Olig2 expression but preserved p75 expression and the spindle morphology of Schwann cells. Preservation of Schwann cell identity in vitro therefore requires signalling cues, including BMP4, presented by peripheral neurons.