Notch signaling mediates the switch to fate commitment of bone marrow-derived Schwann cells

Abstract

Our strategy of deriving Schwann cells from bone marrow stromal cells (Shea et al., 2010) exploits dorsal root ganglia (DRG) neurons to provide Schwann cell-like cells with juxtacrine signals for commitment to the Schwann cell fate. In our search for the signals, immunocytochemical analysis found DLL-1 and Jagged-1, localized on the surface of the DRG neurons whereas the receptor, Notch-1, on bone marrow-derived Schwann cell-like cells. In cocultures with DRG neurons, Schwann cell-like cells were identifiable with nuclear localization of the Notch intracellular domain (NICD). Concomitantly, progressive increase in ErbB2/B3 expression was revealed by immunocytochemistry and Western blotting. As cells achieved commitment to the Schwann cell fate, nuclear NICD was found to return to basal level. Altogether, Notch-ligand interaction between Schwann cell-like cells and DRG neurons in contact are therefore implicated in signalling events that accomplish commitment to the Schwann cell fate in vitro.