Abstract
BackgroundNeural induction is a complex process and the detailed mechanism of FGF-induced neurogenesis remains unclear.MethodsBy using a serum-free neural induction method, we showed that FGF1 dose-dependently promoted the induction of Sox1/N-cadherin/nestin triple positive cells, which represent primitive neuroblasts, from mouse embryonic stem (ES) cells.ResultsWe demonstrated that FGF1, FGF2, and FGF4, but not FGF8b, enhanced this neurogenesis. Especially, FGF-enhanced neurogenesis is not mediated through the rescue of the apoptosis or the enhancement of the proliferation of Sox1+ cells. We further indicated that the inactivation of c-Jun N-terminal kinase-1 (JNK-1) and extracellular signal-related kinase-2 (ERK-2), but not p38 mitogen-activated protein kinase (MAPK), inhibited the neural formation through the inhibition of ES differentiation, but not through the formation of endomesodermal cells.ConclusionsThese lines of evidence delineated the roles of FGF downstream signals in the early neural differentiation of ES cells.
Highlights
Neural induction is a complex process and the detailed mechanism of FGF-induced neurogenesis remains unclear
FGF1 enhanced the generation of Sox1+ cells from embryonic stem (ES) cells Two germline-transmissible mouse ES cell lines, ESC 26 and Sox1-GFP knock-in cells (46C), were used in this study and the ESC 26 cell was characterized with the expression of pluripotent makers (Fig. 1B to 1D)
ES cells were cultured at 2 × 106 cells/10 ml in a defined, serum-free, neural differentiation medium (SFEB method) (Fig. 1A), which is an efficient neural induction method with rare mesendoderm formation [15]
Summary
Neural induction is a complex process and the detailed mechanism of FGF-induced neurogenesis remains unclear. In the early gastrula of the chicken, temporary treatment of the primitive ectoderm with Hensen's node for 5 hours steers the ectoderm to become the neural fate [1,2]. FGF was shown to be responsible for this instructive ability of node and for the maintenance of later neural instructive signals [3,4]. In Xenopus, the study of neural induction has revealed the essential role of Ras/MAPK activation for neurogenesis in uncommitted ectoderm and in dissociated animal cap cells, suggesting that the requirement of FGF signals in neural induction is conserved in chordates [5].
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