成体干细胞神经发生中 FGF 信号的作用

BACKGROUND

Neural induction is a complex process and the detailed mechanism of FGF-induced neurogenesis remains unclear.

METHODS

By 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.

RESULTS

We 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.

CONCLUSIONS

These lines of evidence delineated the roles of FGF downstream signals in the early neural differentiation of ES cells.

背景

神经诱导是一个复杂的过程，FGF 诱导神经发生的详细机制仍不清楚。

方法

通过使用无血清神经诱导方法，我们表明 FGF1 呈剂量依赖性地促进 Sox1/N-钙黏蛋白/巢蛋白三重阳性细胞的诱导，这些细胞代表原始神经母细胞，来自小鼠胚胎干细胞（ES）细胞。

结果

我们证明 FGF1、FGF2 和 FGF4，但不是 FGF8b，增强了这种神经发生。特别是，FGF 增强的神经发生不是通过挽救凋亡或增强 Sox1+细胞的增殖来介导的。我们进一步表明，c-Jun N 末端激酶-1（JNK-1）和细胞外信号相关激酶-2（ERK-2）的失活，但不是 p38 丝裂原活化蛋白激酶（MAPK），通过抑制 ES 分化而不是通过形成内胚层和中胚层细胞来抑制神经形成。