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PMID: 14701872 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Integration of IGF, FGF, and anti-BMP signals via Smad1 phosphorylation in neural induction.

Genes & development ·Vol. 17 ·No. 24 ·2003-12-15 ·Pages 3023-8

Pera EM, Ikeda A, Eivers E, De Robertis EM

Abstract

How do very diverse signaling pathways induce neural differentiation in Xenopus? Anti-BMP (Chordin), FGF8, and IGF2 signals are integrated in the embryo via the regulation of Smad1 phosphorylation. Neural induction results from the combined inhibition of BMP receptor serine/threonine kinases and activation of receptor tyrosine kinases that signal through MAPK and phosphorylate Smad1 in the linker region, further inhibiting Smad1 transcriptional activity. This hard-wired molecular mechanism at the level of the Smad1 transcription factor may help explain the opposing activities of IGF, FGF, and BMP signals not only in neural induction, but also in other aspects of vertebrate development.

MeSH Terms
Animals Bone Morphogenetic Protein Receptors Bone Morphogenetic Proteins/metabolism DNA-Binding Proteins/metabolism Embryo, Nonmammalian Embryonic Induction Fibroblast Growth Factor 8 Fibroblast Growth Factors/pharmacology Insulin-Like Growth Factor II/pharmacology Mice Mitogen-Activated Protein Kinases/metabolism NIH 3T3 Cells Neoplasm Proteins/pharmacology Nervous System/embryology Phosphorylation Receptors, Growth Factor/antagonists & inhibitors Signal Transduction Smad Proteins Smad1 Protein Trans-Activators/metabolism Transcriptional Activation Xenopus Proteins Xenopus laevis
Chemicals
Bone Morphogenetic Proteins DNA-Binding Proteins Fgf8 protein, mouse MXD1 protein, Xenopus Neoplasm Proteins Receptors, Growth Factor Smad Proteins Smad1 Protein Smad1 protein, mouse Trans-Activators Xenopus Proteins Fibroblast Growth Factor 8 Fibroblast Growth Factors Insulin-Like Growth Factor II Mitogen-Activated Protein Kinases Bone Morphogenetic Protein Receptors
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Pera Edgar M
Howard Hughes Medical Institute and Department of Biological Chemistry, University of California-Los Angeles, Los Angeles, CA 90095-1662, USA.
Ikeda Atsushi
Eivers Edward
De Robertis Eddy M
References (30)
30 references, click to expand
  1. Neural induction.
    Annu Rev Cell Dev Biol. 1999;15:411-33 PMID: 10611968
  2. A mechanism of repression of TGFbeta/ Smad signaling by oncogenic Ras.
    Genes Dev. 1999 Apr 1;13(7):804-16 PMID: 10197981
  3. FGF signaling and the anterior neural induction in Xenopus.
    Dev Biol. 1999 Dec 15;216(2):561-81 PMID: 10642793
  4. Dorsal and intermediate neuronal cell types of the spinal cord are established by a BMP signaling pathway.
    Development. 2000 Mar;127(6):1209-20 PMID: 10683174
  5. Controlling TGF-beta signaling.
    Genes Dev. 2000 Mar 15;14(6):627-44 PMID: 10733523
  6. An early requirement for FGF signalling in the acquisition of neural cell fate in the chick embryo.
    Curr Biol. 2000 Apr 20;10(8):421-9 PMID: 10801412
  7. Bmp4 and Fgf10 play opposing roles during lung bud morphogenesis.
    Development. 2000 Jun;127(12):2695-704 PMID: 10821767
  8. Neural induction.
    Curr Opin Genet Dev. 2000 Aug;10(4):357-62 PMID: 10889069
  9. Initiation of neural induction by FGF signalling before gastrulation.
    Nature. 2000 Jul 6;406(6791):74-8 PMID: 10894544
  10. FGF-8 stimulates neuronal differentiation through FGFR-4a and interferes with mesoderm induction in Xenopus embryos.
    Curr Biol. 2000 Nov 30;10(23):1511-4 PMID: 11114518
  11. The establishment of Spemann's organizer and patterning of the vertebrate embryo.
    Nat Rev Genet. 2000 Dec;1(3):171-81 PMID: 11252746
  12. Oncogenic kinase signalling.
    Nature. 2001 May 17;411(6835):355-65 PMID: 11357143
  13. Neural induction: toward a unifying mechanism.
    Nat Neurosci. 2001 Nov;4 Suppl:1161-8 PMID: 11687825
  14. Neural and head induction by insulin-like growth factor signals.
    Dev Cell. 2001 Nov;1(5):655-65 PMID: 11709186
  15. Beta-catenin, MAPK and Smad signaling during early Xenopus development.
    Development. 2002 Jan;129(1):37-52 PMID: 11782399
  16. The IGF pathway regulates head formation by inhibiting Wnt signaling in Xenopus.
    Dev Biol. 2002 Apr 15;244(2):407-17 PMID: 11944947
  17. The role of growth factors in tooth development.
    Int Rev Cytol. 2002;217:93-135 PMID: 12019566
  18. Induction and initial patterning of the nervous system - the chick embryo enters the scene.
    Curr Opin Genet Dev. 2002 Aug;12(4):447-51 PMID: 12100891
  19. Nuclear exclusion of Smad2 is a mechanism leading to loss of competence.
    Nat Cell Biol. 2002 Jul;4(7):519-22 PMID: 12068307
  20. The secreted Frizzled-related protein Sizzled functions as a negative feedback regulator of extreme ventral mesoderm.
    Development. 2003 Feb;130(4):805-16 PMID: 12506010
  21. The BMP antagonist noggin regulates cranial suture fusion.
    Nature. 2003 Apr 10;422(6932):625-9 PMID: 12687003
  22. Evidence for antagonism of BMP-4 signals by MAP kinase during Xenopus axis determination and neural specification.
    Differentiation. 2003 Sep;71(7):434-44 PMID: 12969336
  23. Gastrulation and larval pattern in Xenopus after blastocoelic injection of a Xenopus-derived inducing factor: experiments testing models for the normal organization of mesoderm.
    Dev Biol. 1989 Feb;131(2):383-400 PMID: 2912801
  24. FGF-4 and BMP-2 have opposite effects on limb growth.
    Nature. 1993 Jan 7;361(6407):68-71 PMID: 8421496
  25. A role for HGF/SF in neural induction and its expression in Hensen's node during gastrulation.
    Development. 1995 Mar;121(3):813-24 PMID: 7720585
  26. Fibroblast growth factor is a direct neural inducer, which combined with noggin generates anterior-posterior neural pattern.
    Development. 1995 Nov;121(11):3627-36 PMID: 8582276
  27. Preventing the loss of competence for neural induction: HGF/SF, L5 and Sox-2.
    Development. 1997 Mar;124(6):1191-202 PMID: 9102306
  28. Comparative effects of insulin on the activation of the Raf/Mos-dependent MAP kinase cascade in vitellogenic versus postvitellogenic Xenopus oocytes.
    Dev Biol. 1997 Aug 1;188(1):122-33 PMID: 9245517
  29. Opposing BMP and EGF signalling pathways converge on the TGF-beta family mediator Smad1.
    Nature. 1997 Oct 9;389(6651):618-22 PMID: 9335504
  30. FGF-8 is associated with anteroposterior patterning and limb regeneration in Xenopus.
    Dev Biol. 1997 Dec 15;192(2):455-66 PMID: 9441681
Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1153603
Published
2003-12-15
Pages
3023-8
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC305254
Subset
IM
Grants
NICHD NIH HHS · R01 HD021502 · United States
NICHD NIH HHS · R37 HD021502 · United States
NICHD NIH HHS · R37 HD021502-17 · United States
NICHD NIH HHS · HD 21502-17 · United States
Corrections
CommentIn
PMID: 14701870
External Links
PubMed source DOI: 10.1101/gad.1153603 PMC Full Text View journal details
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