title: 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.
authors.affiliation: Department of Biological Sciences, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sugiura
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ito
mesh_terms: D000818:Animals; D019070:Cell Lineage; D019902:Chondrocytes / Q000166:cytology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D008636:Mesencephalon / Q000166:cytology*; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics; D009432:Neural Crest / Q000166:cytology*; D009457:Neuroglia / Q000166:cytology; D050784:Proto-Oncogene Protein c-ets-1 / Q000502:physiology*; D034741:RNA, Small Interfering; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C494042:Ets1 protein, mouse; D050784:Proto-Oncogene Protein c-ets-1; D034741:RNA, Small Interfering; D016222:Fibroblast Growth Factor 2; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D048052:Mitogen-Activated Protein Kinase 3