Associated Mechanisms Involved In Neuregulin-Induced Proliferation Of Neural Progenitor Cells And Maturation Of Oligodendrocytes

Nestin-expressing neural progenitor cells (NPCs) have been isolatedfrom hippocampus of brains and propagated with epidermal growth factor(EGF) and basic fibroblast growth factor (bFGF). However, the underlyingsignaling mechanisms regulating NPC proliferation remain elusive. Here weshowed that Neuregulinβ1 (NRG), like bFGF, effectively promoted theproliferation of hippocampus-derived NPCs and maintained the progenitorstates of NPCs. Activation of protein kinase C (PKC), a down-stream effectorof phospholipase C (PLC), with 12-O-tetradecanoylphorbol- 13-acetate (TPA)mimicked the NRG-induced proliferation of NPCs. The synergic effect of TPAplus NRG on neurosphere growth further prompted us to find that NRGinduced NPC propagation through PLC/PKC signaling pathway. ErbB4, animportant functional receptor of NRG, had an interaction with PLCγ1 protein.In addition, inactivation of PLC pathway led to severe proliferativesuppression of NPCs. Our study suggests that activation of PLC/PKCpathway may play an essential role in the NRG-induced proliferation ofhippocampus-derived NPCs.