Transducing the Dpp Morphogen Gradient in the Wing of Drosophila

Abstract

Dpp, a TGFbeta, organizes pattern in the Drosophila wing by acting as a graded morphogen, activating different targets above distinct threshold concentrations. Like other TGFbetas, Dpp appears to induce transcription directly via activation of a SMAD, Mad. However, here we demonstrate that Dpp can also control gene expression indirectly by downregulating the expression of the brinker gene, which encodes a putative transcription factor that functions to repress Dpp targets. The medial-to-lateral Dpp gradient along the anterior-posterior axis is complemented by a lateral-to-medial gradient of Brinker, and the presence of these two opposing gradients may function to allow cells to detect small differences in Dpp concentration and respond by activating different target genes.

Finding partners: How BMPs select their targets

“…3A, top). The gene brinker encodes a repressor of direct BMP target genes transcription (Campbell and Tomlinson, 1999;Jaźwiń ska et al, 1999a,b;Minami et al, 1999) and its widespread expression is controlled by yet to be characterized transcriptional activators (Yao et al, 2008). DPP/BMP signaling alleviates Brinker-mediated repression by inhibiting brinker transcription ( Fig.…”

“…DPP/BMP signaling alleviates Brinker-mediated repression by inhibiting brinker transcription ( Fig. 3A, bottom ;Campbell and Tomlinson, 1999;Jaźwiń ska et al, 1999a,b;Minami et al, 1999). A critical transcription factor mediating this DPP-dependent repression of brinker is the zinc finger DNA-binding protein Schnurri (Shn; German for whiskers; Arora et al, 1995;Grieder et al, 1995;Staehling-Hampton et al, 1995).…”

Opposing inputs by Hedgehog and Brinker define a stripe ofhairyexpression in theDrosophilaleg imaginal disc

“…A potential candidate, the transcriptional repressor of Dpp target genes, Brk (Campbell and Tomlinson, 1999;Jazwinska et al, 1999;Kirkpatrick et al, 2001;Minami et al, 1999;Rushlow et al, 2001;Saller and Bienz, 2001;Sivasankaran et al, 2000;Zhang et al, 2001), is suggested by evidence indicating that Dpp is required to override REPE function. In the wing and leg imaginal discs, brk expression is repressed by and is roughly reciprocal to Dpp signaling.…”

“…However, more recent studies indicate that Dpp also regulates its target genes by blocking expression of a repressor. In imaginal discs, Mad/Med and the zinc-finger protein Shn, repress expression of the brinker (brk) gene (Marty et al, 2000;Muller et al, 2003;Torres-Vazquez et al, 2000), which encodes a direct repressor of Dpp target genes (Campbell and Tomlinson, 1999;Jazwinska et al, 1999;Kirkpatrick et al, 2001;Minami et al, 1999;Rushlow et al, 2001;Saller and Bienz, 2001;Sivasankaran et al, 2000;Zhang et al, 2001). The Brk repressor is distributed in a gradient reciprocal to Dpp signaling and functions to delimit the domains of Dpp target gene expression.…”

bantam microRNA is a negative regulator of the Drosophila decapentaplegic pathway

“…brk encodes a transcriptional repressor and is a key target of the Dpp pathway that is negatively regulated by Dpp signaling throughout embryonic and larval development [56,57]. brk is highly expressed in the lateral regions of the wing disc, forming a gradient reciprocal to the Dpp gradient (Figure 1M).…”