Interaction Between FGF2 And NT3 On Neural Stem Cell Proliferation And Differentiation

During development, NP cells in the hippocampus are exposed to a variety of cues with different effects, which are integrated by NP cells so that an appropriate number of cells are ultimately generated. It is therefore important to understand the antagonism and cooperation between cellular factors and the mechanism underlying. In this dissertation, using an FGF2-dependent rat neurosphere culture system, we found that NT3 inhibited both FGF2-induced neurosphere growth and bromodeoxyuridine (BrdU) incorporation in a dose-dependent manner. U0126, a MEK1/2 inhibitor, and LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, both inhibited BrdU incorporation induced by FGF2, suggesting that the extracellular signal–regulated kinase1/2 (ERK1/2) and PI3K pathways are required for FGF2-induced neural progenitor cell proliferation. We found that NT3 significantly inhibited FGF2-induced phosphorylation of Akt and glycogen synthase kinase3β(GSK3β), a downstream kinase of Akt, whereas NT3 did not affect phosphorylation of ERK1/2. The inhibitory effect of NT3 on FGF2-induced neural progenitor cell proliferation was abolished by LY294002...