Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2009 Oct-Dec;20(5-6):357-65.
doi: 10.1016/j.cytogfr.2009.10.017. Epub 2009 Nov 5.

Integration of BMP and Wnt signaling via vertebrate Smad1/5/8 and Drosophila Mad

Edward Eivers  1 , Hadrien Demagny, E M De Robertis
Affiliations
Review

Integration of BMP and Wnt signaling via vertebrate Smad1/5/8 and Drosophila Mad

Edward Eivers et al. Cytokine Growth Factor Rev. 2009 Oct-Dec.

Abstract

BMPs pattern the dorsal-ventral axis of vertebrate embryos. Smad1/5/8 transduces the BMP signal, and receives phosphorylation inputs from both MAPK and GSK3. Phosphorylation of Smad1 by MAPK and GSK3 result in its polyubiquitination and transport to the centrosome where it is degraded by the proteasome. These linker phosphorylations inhibit BMP/Smad1signaling by shortening its duration. Wnt, which negatively regulates GSK3 activity, prolongs the BMP/Smad1 signal. Remarkably, linker-phosphorylated Smad1 has been shown to be inherited asymmetrically during cell division. Drosophila contains a single Smad1/5/8 homologue, Mad, and is stabilized by phosphorylation-resistant mutations at GSK3 sites, causing Wingless-like effects. We summarize here the significance of linker-phosphorylated Smad1/Mad in relation to signal intensity and duration, and how this integrates the Wnt and BMP pathways during cell differentiation.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Left, expression of Chordin and BMP4 on opposite centers of a Xenopus embryo. Right, model illustrating the two perpendicular morphogenetic gradients of BMP and Wnt. Cells sense their position within these Cartesian-coordinates, which specify their fate in the body plan [4].
Figure 2
Figure 2
Integration of multiple extracellular signaling pathways at the level of Smad1/5/8 phosphorylations. BMP-dependent C-terminal phosphorylation of Smad1, activates target gene expression whereas, MAPK and GSK3 linker-phosphorylations promote degradation terminating the BMP/Smad1 signal. Wnt prolongs BMP signals by inhibiting GSK3 phosphorylation.
Figure 3
Figure 3
(A) Asymmetric distribution of pSmad1 targeted for degradation in self-renewing human embryonic stem cells. (B) When the proteosomal machinery is inhibited pSmad1GSK3 accumulates in a pericentrosomal nuclear bay. (C) Model illustrating asymmetric inheritance of pericentrosomal material (green) during mitosis [58].
Figure 4
Figure 4
Drosophila Mad transduces Wg signals. (A-B) Overexpression of MGM in clones induce duplications, and Mad depletion resulted in loss-of the margin (C) Wild-type cuticle. (D-D′ and E-E′) Lawns of row 5 denticles in Mad RNAi or Wg null cuticles [59].
Figure 5
Figure 5
(A) C3 Xenopus blastomere injection targets somites in Xenopus (B) Normal somite border pattern on injected side. (C) Microinjection of Smad8-MO erase segmental somite borders [59]. (D) Comparison of Smad/Mad linker regulation in vertebrate and Drosophila.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Niehrs C. Regionally specific induction by the Spemann-Mangold organizer. Nat Rev Genet. 2004;6:425–434. - PubMed
    1. De Robertis EM. Spemann's organizer and self-regulation in amphibian embryos. Nat Rev Mol Cell Bio. 2006;7:296–302. - PMC - PubMed
    1. Fuentealba LC, Eivers E, Ikeda A, Hurtado C, Kuroda H, Pera EM, et al. Integrating patterning signals: Wnt/GSK3 regulates the duration of the BMP/Smad1 signal. Cell. 2007;131:980–993. - PMC - PubMed
    1. De Robertis EM. Evo-Devo: variations on ancestral themes. Cell. 2008;132:185–195. - PMC - PubMed
    1. Eivers E, Fuentealba LC, De Robertis EM. Integrating positional information at the level of Smad1/5/8. Curr. Op. Gen Dev. 2008;18:304–10. - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources