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Inhibition of Drosophila Wg Signaling Involves Competition between Mad and Armadillo/β-Catenin for dTcf Binding

By Yi Arial Zeng, Maryam Rahnama, Simon Wang, Wendy Lee and Esther M. Verheyen


Precisely regulated signal transduction pathways are crucial for the regulation of developmental events and prevention of tumorigenesis. Both the Transforming Growth Factor β (TGFβ)/Bone morphogenetic protein (BMP) and Wnt/Wingless (Wg) pathways play essential roles in organismal patterning and growth, and their deregulation can lead to cancers. We describe a mechanism of interaction between Drosophila Wg and BMP signaling in which Wg target gene expression is antagonized by BMP signaling. In vivo, high levels of both an activated BMP receptor and the BMP effector Mad can inhibit the expression of Wg target genes. Conversely, loss of mad can induce Wg target gene expression. In addition, we find that ectopic expression in vivo of the Wg transcription factor dTcf is able to suppress the inhibitory effect caused by ectopic Mad. In vitro binding studies revealed competition for dTcf binding between Mad and the Wnt effector β-catenin/Armadillo (Arm). Our in vivo genetic analyses and target gene studies support a mechanism consistent with the in vitro binding and competition studies, namely that BMP pathway components can repress Wg target gene expression by influencing the binding of Arm and dTcf

Topics: Research Article
Publisher: Public Library of Science
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Provided by: PubMed Central

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  12. (2000). decapentaplegic is a direct target of dTcf repression in the Drosophila visceral mesoderm.
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  14. (1996). decapentaplegic, a target gene of the wingless signalling pathway in the Drosophila midgut.
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  20. (1994). Ectopic decapentaplegic in the Drosophila midgut alters the expression of five homeotic genes, dpp, and wingless, causing specific morphological defects.
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  22. (1995). Genetic characterization and cloning of mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster.
  23. (1997). LEF-1, a nuclear factor coordinating signaling inputs from wingless and decapentaplegic.
  24. (1997). Long-range action of Wingless organizes the dorsal-ventral axis of the Drosophila wing.
  25. (1994). Martinez-Arias A
  26. (2008). Molecular integration of wingless, decapentaplegic, and autoregulatory inputs into Distalless during Drosophila leg development.
  27. (2004). Morphogens, their identification and regulation.
  28. (1997). Negative regulation of Armadillo, a Wingless effector in Drosophila.
  29. (2004). Nemo is an inducible antagonist of Wingless signaling during Drosophila wing development.
  30. (2002). Notch and Wingless modulate the response of cells to Hedgehog signalling in the Drosophila wing.
  31. (1997). pangolin encodes a Lef-1 homologue that acts downstream of Armadillo to transduce the Wingless signal in Drosophila.
  32. (2002). PP1 binds Sara and negatively regulates Dpp signaling in Drosophila melanogaster.
  33. (2002). Pygopus, a nuclear PHD-finger protein required for Wingless signaling in Drosophila.
  34. (2005). Smad transcription factors.
  35. (2003). Smad4 and beta-catenin co-activators functionally interact with lymphoid-enhancing factor to regulate graded expression of Msx2.
  36. (2006). Smad4 cooperates with lymphoid enhancerbinding factor 1/T cell-specific factor to increase c-myc expression in the absence of TGF-beta signaling.
  37. (1993). Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.
  38. (2002). TCF transcription factors, mediators of Wntsignaling in development and cancer.
  39. (1996). The axisinducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3.
  40. (2007). The Decapentaplegic morphogen gradient: from pattern formation to growth regulation.
  41. (1997). The Drosophila mushroom body is a quadruple structure of clonal units each of which contains a virtually identical set of neurones and glial cells.
  42. (2004). The murine gastrin promoter is synergistically activated by transforming growth factor-beta/Smad and Wnt signaling pathways.
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  44. (1998). Tomlinson A
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  46. (2007). Wing vein patterning in Drosophila and the analysis of intercellular signaling.
  47. (2003). Wingless and Notch signaling provide cell survival cues and control cell proliferation during wing development.
  48. (1993). wingless expression mediates determination of peripheral nervous system elements in late stages of Drosophila wing disc development.
  49. (2002). Wnt and Bmp signalling cooperatively regulate graded Emx2 expression in the dorsal telencephalon.
  50. (2006). Wnt/beta-catenin signaling in development and disease.

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