Raf-1 Kinase Is Essential for Early Xenopus Development and Mediates the Induction of Mesoderm by FGF

Cell. 1993 May 7;73(3):571-83. doi: 10.1016/0092-8674(93)90143-e.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Activins
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Calcium / metabolism
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / physiology*
  • Epitopes / analysis
  • Female
  • Fibroblast Growth Factor 2 / pharmacology*
  • Gastrula / cytology
  • Gastrula / drug effects
  • Gastrula / physiology
  • Immunohistochemistry
  • Inhibins / pharmacology
  • Mesoderm / cytology
  • Mesoderm / drug effects
  • Mesoderm / physiology*
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Oocytes / physiology*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-raf
  • RNA / genetics
  • RNA / isolation & purification
  • Regulatory Sequences, Nucleic Acid
  • Xenopus / embryology*

Substances

  • Epitopes
  • Proto-Oncogene Proteins
  • Fibroblast Growth Factor 2
  • Activins
  • Inhibins
  • RNA
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf
  • Calcium