Ribisi S, Mariani F V, Aamar E, Lamb T M, Frank D, Harland R M
Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California, 94720, USA.
Dev Biol. 2000 Nov 1;227(1):183-96. doi: 10.1006/dbio.2000.9889.
Fibroblast growth factor (FGF) has been proposed to be involved in the specification and patterning of the developing vertebrate nervous system. There is conflicting evidence, however, concerning the requirement for FGF signaling in these processes. To provide insight into the signaling mechanisms that are important for neural induction and anterior-posterior neural patterning, we have employed the dominant negative Ras mutant, N17Ras, in addition to a truncated FGF receptor (XFD). Both N17Ras and XFD, when expressed in Xenopus laevis animal cap ectoderm, inhibit the ability of FGF to generate neural pattern. They also block induction of posterior neural tissue by XBF2 and XMeis3. However, neither XFD nor N17Ras inhibits noggin, neurogenin, or XBF2 induction of anterior neural markers. MAP kinase activation has been proposed to be necessary for neural induction, yet N17Ras inhibits the phosphorylation of MAP kinase that usually follows explantation of explants. In whole embryos, Ras-mediated FGF signaling is critical for the formation of posterior neural tissues but is dispensable for neural induction.
成纤维细胞生长因子(FGF)被认为参与了发育中的脊椎动物神经系统的特化和模式形成。然而,关于这些过程中FGF信号传导的必要性,存在相互矛盾的证据。为了深入了解对神经诱导和前后神经模式形成重要的信号传导机制,除了截短的FGF受体(XFD)外,我们还使用了显性负性Ras突变体N17Ras。当N17Ras和XFD在非洲爪蟾动物帽外胚层中表达时,它们都会抑制FGF产生神经模式的能力。它们还会阻断XBF2和XMeis3对后神经组织的诱导。然而,XFD和N17Ras都不会抑制头蛋白、神经生成素或XBF2对头神经标记物的诱导。有人提出MAP激酶激活对于神经诱导是必要的,但N17Ras会抑制通常在植入外植体后发生的MAP激酶磷酸化。在完整胚胎中,Ras介导的FGF信号传导对于后神经组织的形成至关重要,但对于神经诱导是可有可无的。