Roles of Ets-1 and p70S6 kinase in chondrogenic and gliogenic specification of mouse mesencephalic neural crest cells

Abstract

Fibroblast growth factors (FGFs) have been shown to promote the chondrogenic and gliogenic specification of mouse mesencephalic neural crest cells through Notch signaling [Nakanishi, K., Chan, S.Y., Ito, K., 2007. Notch signaling is required for the chondrogenic specification of mouse mesencephalic neural crest cells. Mech. Dev. 124, 190–203; Ijuin, K., Nakanishi, K., Ito, K., 2008. Different downstream pathways for Notch signaling are required for gliogenic and chondrogenic specification of mouse mesencephalic neural crest cells. Mech. Dev. 125, 462–474]. In the present study, we analyzed FGF signaling pathways in chondrogenic and gliogenic specification. The promotion of chondrogenesis by FGF-2 was significantly suppressed by U0126, an inhibitor of the extracellular signal-regulated protein kinase (Erk) pathway, and by Erk-1 siRNA. Chondrogenesis was also prevented by the dominant negative Ets-1 expression vector. In contrast, Ets-1 was irrelevant to gliogenesis. The promotion of gliogenesis by FGF-2 was not only inhibited by U0126 but also by LY294002 and rapamycin, inhibitors of the Akt pathway, and by Akt-1 siRNA. Furthermore, gliogenesis was dramatically prevented by blocking the expression of p70S6 kinase (p70S6k), which is activated by both the Erk and Akt pathways, with p70S6k siRNA. These results suggest that Ets-1 activated by the Erk pathway promotes chondrogenic specification and p70S6k activated by both the Erk and Akt pathways plays an important role in gliogenic specification.