Mesoderm induction in Xenopus caused by activation of MAP kinase

Umbhauer, Muriel; Marshall, Christopher J.; Mason, Clive; Old, Robert; Smith, James C.

doi:10.1038/376058a0

Cited by 215 publications

(150 citation statements)

References 32 publications

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“…Concomitant decrease of Akt/PKB and PLCg-1 activation in the mutant connects FGF signaling and epithelial di erentiation with the PI 3-kinase pathway. Comparing Akt/PKB and PLCg-1 activation with the activation of MAPK/Erk, the major signal transduction pathway of FGF signaling during gastrulation (Northrop et al, 1995;Umbhauer et al, 1995), suggested that the PI 3-kinase pathway may have a special role in the early epithelial di erentiation of the embryoid body.…”

Section: Discussionmentioning

confidence: 99%

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Fibroblast growth factor (FGF) signaling through PI 3-kinase and Akt/PKB is required for embryoid body differentiation

et al. 2000

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The role of FGF signaling in early epithelial di erentiation was investigated in ES (embryonic stem) cell derived embryoid bodies. A dominant negative ®broblast growth factor receptor (FGFR) mutation was created by stably introducing into ES cells an Fgfr2 cDNA, truncated in its enzymatic domains. These cells failed to di erentiate into cystic embryoid bodies. No epithelial di erentiation and cavitation morphogenesis could be observed, in the mutant, although its rate of cell proliferation remained unchanged. This phenotype was associated with a signi®cant decrease in the activation of Akt/PKB and PLCg-1, as compared to the wild type, while the activation of MAPK/Erk was less a ected. Requirement for PI 3-kinase signaling in embryoid body di erentiation was demonstrated by speci®c inhibitors. Akt/PKB activation was abrogated by wortmannin in short-term experiments. In long-term cultures Ly294002 inhibited the di erentiation of ES cells into embryoid bodies. Our data demonstrate that for early epithelial di erentiation FGF signaling is required through the PI 3-kinase-Akt/ PKB pathway.

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Section: Discussionmentioning

confidence: 99%

“…A leading role is attributed to the MAPK/ERK pathway, in insect (Gabay et al, 1997) and vertebrate development (Northrop et al, 1995;Umbhauer et al, 1995). Another signaling pathway, that leads through phosphatidyl-inositol 3-kinase (PI 3-kinase) and Akt/PKB, is also induced by the same receptors.…”

Section: Introductionmentioning

confidence: 99%

Fibroblast growth factor (FGF) signaling through PI 3-kinase and Akt/PKB is required for embryoid body differentiation

et al. 2000

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“…Blocking the function of Ras, Raf, MEK and ERK inhibits mesoderm formation. Overexpression of the constitutively activated forms of these signaling components induces the expression of mesodermal markers in an animal cap assay (Whitman & Melton 1992;MacNicol et al 1993;LaBonne & Whitman 1994;Gotoh et al 1995;LaBonne et al 1995;Umbhauer et al 1995). A recent study has suggested that the spatial pattern of ERK activation closely resembles the expression of FGF (Christen & Slack 1999).…”

Section: Introductionmentioning

confidence: 99%

Role of the FGF and MEK signaling pathway in the ascidian embryo

2001

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In the ascidian embryo, a fibroblast growth factor (FGF)-like signal from presumptive endoderm blastomeres between the 32-cell and early 64-cell stages induces the formation of notochord and mesenchyme cells. However, it has not been known whether endogenous FGF signaling is involved in the process. Here it is shown that 64-cell embryos exhibit a marked increase in endogenous extracellular signal-regulated kinase (ERK/MAPK) activity. The increase in ERK activity was reduced by treatment with an FGF receptor 1 inhibitor, SU5402, and a MEK (ERK kinase/MAPKK) inhibitor, U0126. Both drugs blocked the formation of notochord and mesenchyme when embryos were treated at the 32-cell stage, but not at the 2-or 110-cell stages. The dominant-negative form of Ras also suppressed notochord and mesenchyme formation. Both inhibitors suppressed induction by exogenous basic FGF. These results suggest that the FGF signaling cascade is indeed necessary for the formation of notochord and mesenchyme cells during ascidian embryogenesis. It is also shown that FGF signaling is required for formation of the secondary notochord, secondary muscle and neural tissues, and at least ERK activity is necessary for the formation of trunk lateral cells and posterior endoderm. Therefore, FGF and MEK signaling are required for the formation of various tissues in the ascidian embryo.

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“…Several groups have shown that mesoderm induction by FGF in Xenopus embryogenesis requires activation of the MAPK pathway (Gotoh et al, 1995b;LaBonne et al, 1995;Umbhauer et al, 1995). We considered two explanations for our ®nding that only DN Grb2 mutants could inhibit Erk1 activation in 293 cells (data not shown), while NckKSH2 as well as the DN Grb2 mutants could inhibit the induction of a mesodermspeci®c gene in Xenopus animal caps (Figure 1b).…”

Section: E Ect Of Dn Adapters On Erk1 Induction By Efgf In 293 Cells mentioning

confidence: 84%

“…Microinjection of RNA encoding dominantnegative mutants of Ras or Raf, or encoding a MAPKspeci®c phosphatase, into Xenopus embryos has also implicated Ras, Raf and MAPK in mesoderm induction by FGF (Gotoh et al, 1995b;LaBonne et al, 1995;MacNicol et al, 1993;Umbhauer et al, 1995;Whitman and Melton, 1992). Although a peptide fragment of the chicken bFGFR was shown to bind to the SH2 domain of Grb2 with moderate a nity (Ward et al, 1996), intact FGFRs do not bind directly to SH2/SH3 adapter proteins.…”

Section: Introductionmentioning

confidence: 99%

Dominant-negative mutants of the SH2/SH3 adapters Nck and Grb2 inhibit MAP kinase activation and mesoderm-specific gene induction by eFGF in Xenopus

Gupta

Mayer

1998

Oncogene

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The SH2/SH3 adapters Nck, Grb2 and Crk promote the assembly of signaling complexes by binding to tyrosine phosphorylated proteins using their SH2 domains and to proline-rich sequences on e ector molecules using their SH3 domains. FGF, which activates a receptor tyrosine kinase, induces mesoderm formation in Xenopus embryos through activation of the Ras/Raf/MAPK signaling pathway. We present evidence that dominant-negative mutants of Nck and Grb2, but not Crk1, can inhibit mesoderm-speci®c gene induction by eFGF in Xenopus animal cap explants. We also show that dominantnegative mutants of Grb2 and Nck can inhibit eFGFinduced Erk1 activation in Xenopus animal caps, and that targeting the ®rst two SH3 domains of Nck to the membrane can activate Erk1 in the absence of eFGF. Furthermore, combinations of the dominant-negative Grb2 mutants with the inhibitory Nck mutant synergistically inhibited Erk1 activation by eFGF in Xenopus animal caps, suggesting that the dominant-negative Nck and Grb2 mutants inhibit Erk1 activation by binding to di erent proteins. By contrast only Grb2 mutants could inhibit eFGF-induced Erk1 activation in human 293 cells, demonstrating diversity in the speci®c mechanisms of signaling from FGF to MAP kinases in di erent cells.

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Mesoderm induction in Xenopus caused by activation of MAP kinase

Cited by 215 publications

References 32 publications

Fibroblast growth factor (FGF) signaling through PI 3-kinase and Akt/PKB is required for embryoid body differentiation

Fibroblast growth factor (FGF) signaling through PI 3-kinase and Akt/PKB is required for embryoid body differentiation

Role of the FGF and MEK signaling pathway in the ascidian embryo

Dominant-negative mutants of the SH2/SH3 adapters Nck and Grb2 inhibit MAP kinase activation and mesoderm-specific gene induction by eFGF in Xenopus

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