Drosophila Mad binds to DNA and directly mediates activation of vestigial by Decapentaplegic

Nature. 1997 Jul 17;388(6639):304-8. doi: 10.1038/40906.


The TGF-beta (transforming growth factor-beta)-related signalling proteins, including Decapentaplegic (Dpp) in Drosophila-and bone morphogenic proteins and activin in vertebrates, affect the growth and patterning of a great variety of structures. However, the mechanisms by which these ligands regulate gene expression are not understood. Activation of complexes of type I with type II receptors results in the phosphorylation and nuclear localization of members of the SMAD protein family, which are thought to act as co-activators of transcription, perhaps in conjunction with sequence-specific cofactors. Here we show that the amino-terminal domain of the Drosophila Mothers against dpp protein (Mad), a mediator of Dpp signalling, possesses a sequence-specific DNA-binding activity that becomes apparent when carboxy-terminal residues are removed. Mad binds to and is required for the activation of an enhancer within the vestigial wing-patterning gene in cells across the entire developing wing blade. Mad also binds to Dpp-response elements in other genes. These results suggest that Dpp signalling regulates gene expression by activating Mad binding to target gene enhancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Consensus Sequence
  • DNA / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Drosophila / embryology
  • Drosophila / genetics
  • Drosophila Proteins*
  • Embryonic Induction
  • Enhancer Elements, Genetic
  • Female
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / genetics
  • Insect Proteins / genetics
  • Insect Proteins / metabolism*
  • Male
  • Nuclear Proteins / genetics*
  • Protein Binding
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins*
  • Signal Transduction
  • Transcription Factors*
  • Wings, Animal / embryology


  • DNA-Binding Proteins
  • Drosophila Proteins
  • Homeodomain Proteins
  • Insect Proteins
  • MAD protein, Drosophila
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Transcription Factors
  • Ubx protein, Drosophila
  • dpp protein, Drosophila
  • lab protein, Drosophila
  • vg protein, Drosophila
  • DNA