Instructive role of DRG neurons in derivation of schwann cells from bone marrow stromal cells

Abstract

Our strategy in in vitro differentiation of Schwann cells from bone marrow stromal cells (BMSCs) of adult rats exploits purified embryonic dorsal root ganglia (DRG) neurons to co-culture with Schwann cell-like cells (SCLCs) derived from BMSCs. We hypothesize that juxtacrine signaling cues provided by DRG neurons mediate the commitment to the Schwann cell fate. In search of the signals, we found that both Notch ligands and neuregulin-1 type III were localized on the surface of DRG neurons. Notch-1 receptor was detectable on the surface of SCLCs, but the ErbB2/3 heterodimeric receptors of neuregulin were barely detectable. In cocultures, Notch ligand-receptor interaction between DRG neurons and SCLCs led to an increase in ErbB2/B3 expression in SCLCs and eventual attainment of the Schwann cell fate. Treatment of co-cultures with Notch inhibitor DAPT in SCLCs deterred not only the increase in ErbB2/3 expression, but also the progress of SCLCs to the Schwann cell fate. Taken together, the juxtacrine signalling via Notch contribute to the upregulation of ErbB receptors for neuregulin-driven commitment of SCLCs to the Schwann cell fate.