Wingless directly represses DPP morphogen expression via an armadillo/TCF/Brinker complex

PLoS One. 2007 Jan 3;2(1):e142. doi: 10.1371/journal.pone.0000142.


Background: Spatially restricted morphogen expression drives many patterning and regeneration processes, but how is the pattern of morphogen expression established and maintained? Patterning of Drosophila leg imaginal discs requires expression of the DPP morphogen dorsally and the wingless (WG) morphogen ventrally. We have shown that these mutually exclusive patterns of expression are controlled by a self-organizing system of feedback loops that involve WG and DPP, but whether the feedback is direct or indirect is not known.

Methods/findings: By analyzing expression patterns of regulatory DNA driving reporter genes in different genetic backgrounds, we identify a key component of this system by showing that WG directly represses transcription of the dpp gene in the ventral leg disc. Repression of dpp requires a tri-partite complex of the WG mediators armadillo (ARM) and dTCF, and the co-repressor Brinker, (BRK), wherein ARM.dTCF and BRK bind to independent sites within the dpp locus.

Conclusions/significance: Many examples of dTCF repression in the absence of WNT signaling have been described, but few examples of signal-driven repression requiring both ARM and dTCF binding have been reported. Thus, our findings represent a new mode of WG mediated repression and demonstrate that direct regulation between morphogen signaling pathways can contribute to a robust self-organizing system capable of dynamically maintaining territories of morphogen expression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Armadillo Domain Proteins / genetics
  • Armadillo Domain Proteins / metabolism*
  • Body Patterning / physiology
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / anatomy & histology
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / physiology*
  • Enhancer Elements, Genetic
  • Gene Expression Regulation, Developmental*
  • Genes, Reporter
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Signal Transduction / physiology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Wnt1 Protein / genetics
  • Wnt1 Protein / metabolism*


  • ARM protein, Drosophila
  • Armadillo Domain Proteins
  • Drosophila Proteins
  • Multiprotein Complexes
  • Repressor Proteins
  • Transcription Factors
  • Wnt1 Protein
  • brk protein, Drosophila
  • dpp protein, Drosophila
  • pan protein, Drosophila
  • wg protein, Drosophila