AP-1 JUN IS REQUIRED FOR EARLY XENOPUS DEVELOPMENT AND MEDIATES MESODERM INDUCTION BY FIBROBLAST GROWTH-FACTOR BUT NOT BY ACTIVIN/

In Xenopus, normal mesoderm formation depends on signaling through the fibroblast growth factor (FGF) tyrosine kinase receptor. An important signaling pathway from receptor tyrosine kinases involves Ras/Raf/MAP kinase, However, the downstream pathway that occurs in the nucleus to finally trigger gene expression for mesoderm formation remains unknow n, We report here that a high level of activator protein-1 (AP-1)-depe ndent transcriptional activity is detected during the early developmen t of Xenopus embryos. Injection of a dominant negative mutant jun (DNM -jun or TAM67) RNA into the two-cell stage embryos inhibited endogenou s AP-1 activity and blocked normal embryonic development with severe p osterior truncation in tadpoles. The inhibition of AP-1 activity and t he phenotypic change induced by TAM67 was rescued by co-injection of w ild-type c-jun RNA, but not by the control beta-galactosidase RNA. The FGF-stimulated mesoderm induction was markedly inhibited in animal ca p explants from the embryos injected with TAM67. Activin induction of mesoderm, on the other hand, was normal in the embryos injected with T AM67 RNA. These findings suggest that AP-1 mediates FGF, but not activ in, receptor signaling during mesoderm induction and the AP-1/Jun is a key signaling molecule in the development of posterior structure.