Mesoderm induction in Xenopus caused by activation of MAP kinase.
Mesoderm induction is a critical early step in vertebrate development, involving changes in gene expression and morphogenesis. In Xenopus, normal mesoderm formation depends on signalling through the fibroblast growth factor (FGF) tyrosine kinase receptor. One important signalling pathway from receptor tyrosine kinases involves p21ras (ref. 5). Ras associates with the serine kinase c-Raf-1 in a GTP-dependent manner, and this complex phosphorylates and activates MAPK/ERK kinase (MEK), a protein kinase with dual specificity. MEK then activates p42mapk and (at least in mammals) p44mapk, members of the mitogen-activated protein (MAP) kinase family. FGF activates MAP kinase during mesoderm induction, and the use of dominant-negative constructs suggests that mesoderm induction by FGF requires both Ras and Raf. However, these experiments do not reveal whether Ras and Raf do act through MAP kinase to induce mesoderm or whether another pathway, such as the phosphatidylinositol 3-kinase cascade, is involved. Here we show that expression of active forms of MEK or of MAP kinase induces ventral mesoderm of the kind elicited by FGF. Overexpression of a Xenopus MAP kinase phosphatase blocks mesoderm induction by FGF, and causes characteristic defects in mesoderm formation in intact embryos, whereas inhibition of the P13 kinase and p70 S6 kinase pathways has no effect on mesoderm induction by FGF. FGF induces different types of mesoderm in a dose-dependent manner; strikingly, this is mimicked by expressing different levels of activated MEK. Together, these experiments demonstrate that activation of MAP kinases is necessary and sufficient for mesoderm formation.
Umbhauer
M
M
Division of Developmental Biology, National Institute for Medical Research, London, UK.
Marshall
C J
CJ
Mason
C S
CS
Old
R W
RW
Smith
J C
JC
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D001483:Base Sequence; D001755:Blastocyst / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004627:Embryonic Induction; D004789:Enzyme Activation; D005326:Fetal Proteins / Q000096:biosynthesis; D005346:Fibroblast Growth Factors / Q000502:physiology; D008648:Mesoderm / Q000201:enzymology / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D012313:RNA / Q000235:genetics; D020825:T-Box Domain Proteins; D014981:Xenopus; D000098908:Brachyury Protein
D000199:Actins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D017931:DNA Primers; D004268:DNA-Binding Proteins; D005326:Fetal Proteins; D005346:Fibroblast Growth Factors; D019950:Mitogen-Activated Protein Kinase 1; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D017027:Protein Tyrosine Phosphatases; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D019908:Proto-Oncogene Proteins c-raf; D016283:Proto-Oncogene Proteins p21(ras); D012313:RNA; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein