Raf-1 kinase is essential for early Xenopus development and mediates the induction of mesoderm by FGF.
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.
MacNicol
A M
AM
Howard Hughes Medical Institute, University of California, San Francisco 94143.
Muslin
A J
AJ
Williams
L T
LT
D028341:Activins; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology*; D000939:Epitopes / Q000032:analysis; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005775:Gastrula / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D007265:Inhibins / Q000494:pharmacology; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012045:Regulatory Sequences, Nucleic Acid; D014981:Xenopus / Q000196:embryology*
D000939:Epitopes; D011518:Proto-Oncogene Proteins; D016222:Fibroblast Growth Factor 2; D028341:Activins; D007265:Inhibins; D012313:RNA; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D002118:Calcium