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(1), In Xenopus , normal mesoderm formation depends on signalling through the fibrobla st growth factor (FGF) tyrosine kinase receptor(2-4). One important si gnalling pathway from receptor tyrosine kinases involves p21(ras) (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 p42 (mapk); and (at least in mammals) p44(mapk), members of the mitogen-ac tivated protein (MAP) kinase family(6), FGF activates MAP kinase durin g mesoderm induction(7-9), and the use of dominant-negative constructs suggests that mesoderm induction by FGF requires both Res and Raf(10, 11). However, these experiments Bo not reveal whether Ras and Raf do a ct through MAP kinase to induce mesoderm or whether another pathway, s uch as the phosphatidylinositol 3-kinase cascade(12), is involved. Her e we show that expression of active forms of MEK or of MAP kinase indu ces ventral mesoderm of the hind elicited by FGF, Overexpression of a Xenopus MAP kinase phosphatase Mocks mesoderm induction by FGF, and ca uses characteristic defects in mesoderm formation in intact embryos, w hereas inhibition of the P13 kinase and p70 S6 kinase pathways has no effect on mesoderm induction by FGF, FGF induces different types of me soderm in a dose-dependent manner(13); strikingly, this is mimicked by expressing different levels of activated MEK. Together, these experim ents demonstrate that activation of MAP kinases is necessary and suffi cient for mesoderm formation.