MacNicol A M, Muslin A J, Williams L T
Howard Hughes Medical Institute, University of California, San Francisco 94143.
Cell. 1993 May 7;73(3):571-83. doi: 10.1016/0092-8674(93)90143-e.
Animal cap explants from Xenopus embryos injected with a dominant negative Raf-1 mutant, termed NAF (not a functional Raf), demonstrated a complete block to basic fibroblast growth factor (FGF)-stimulated mesoderm induction. Activin induction of mesoderm was normal in embryos that expressed NAF. Injection of NAF RNA into 2-cell stage embryos blocked normal development during neurula stages and caused severe posterior truncations in tadpoles. The phenotype induced by NAF could be rescued by coinjection of wild-type raf-1 RNA. The NAF mutant functioned by specifically blocking the activation of endogenous Raf kinase activity. These findings suggest that Raf-1 mediates FGF, but not activin, receptor signaling during mesoderm induction and implicate Raf-1 as a key signaling molecule in the development of posterior structure.
用一种显性负性Raf-1突变体(称为NAF,即无功能的Raf)注射非洲爪蟾胚胎后获得的动物帽外植体,显示出对碱性成纤维细胞生长因子(FGF)刺激的中胚层诱导的完全阻断。在表达NAF的胚胎中,激活素诱导中胚层正常。将NAF RNA注射到二细胞期胚胎中会阻断神经胚期的正常发育,并导致蝌蚪严重的后部截断。NAF诱导的表型可通过共注射野生型raf-1 RNA来挽救。NAF突变体通过特异性阻断内源性Raf激酶活性的激活来发挥作用。这些发现表明,Raf-1在中胚层诱导过程中介导FGF而非激活素的受体信号传导,并暗示Raf-1是后部结构发育中的关键信号分子。