Juxtacrine signalling via Notch and ErbB receptors in the switch to fate commitment of bone marrow-derived Schwann cells

Abstract

Our strategy of deriving Schwann cells from bone marrow stromal cells exploits purified dorsal root ganglia (DRG) neurons to provide Schwann cell-like cells (SCLCs) with juxtacrine signals that mediate commitment to the Schwann cell fate. In search for the signals, we found both Notch ligands and neuregulin-1 type III localized on the surface of DRG neurons. Immunopositivity for cell surface Notch-1 receptor was detectable on bone marrow-derived SCLCs but the ErbB2/3 heterodimeric receptors of neuregulin-1 were barely detectable. In co-cultures, the Notch ligands on DRG neurons triggered nuclear translocation of Notch intracellular domain (NICD), corresponding increase in ErbB2/3 expression in the SCLCs and attainment of the Schwann cell fate. Treatment of co-cltures with DAPT or a DLL-1 blocking peptide to perturb Notch signaling deterred not only the increase in ErbB2/B3 expression in SCLCs but also the progress of SCLCs to the Schwann cell fate. We conclude that juxtacrine signalling via Notch plays a key role in the upregulation of ErbB receptors for neuregulin-driven commitment of SCLCs to the Schwann cell fate.