Abstract
BackgroundSpatially 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/FindingsBy 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/SignificanceMany 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.
Highlights
Numerous studies have demonstrated that WNT signaling (WG in Drosophila) mobilizes a nuclear b-catenin/TCF complex that can activate transcription of WNT target genes [1,2,3,4]
We and others have noted that WNT/ WG signaling activates wg expression and represses dpp expression in the ventral territory of the Drosophila leg imaginal disc, and this is critical for normal patterning of the disc [6,7,8,9,10,11], but whether WNT/WG directs ARMNdTCF complexes to activate expression of repressor proteins or whether ARMNdTCF complexes bind directly to the dpp gene to repress transcription is unclear
To determine whether repression by WG signaling is direct or indirect and to better understand the factors that allow a WG signal to be inhibitory, we investigated whether dTCF binds to the dpp gene and whether dTCF and/or ARM are required for WG directed repression
Summary
Numerous studies have demonstrated that WNT signaling (WG in Drosophila) mobilizes a nuclear b-catenin/TCF complex that can activate transcription of WNT target genes [1,2,3,4]. Development of the Drosophila leg imaginal disc requires maintaining complementary territories of dorsal dpp and ventral wg morphogen expression. We and others have noted that WNT/ WG signaling activates wg expression and represses dpp expression in the ventral territory of the Drosophila leg imaginal disc, and this is critical for normal patterning of the disc [6,7,8,9,10,11], but whether WNT/WG directs ARMNdTCF complexes to activate expression of repressor proteins or whether ARMNdTCF complexes bind directly to the dpp gene to repress transcription is unclear. 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
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