The Drosophila Gene brinker Reveals a Novel Mechanism of Dpp Target Gene Regulation

Abstract

decapentaplegic (dpp), a Drosophila member of the TGFbeta family of secreted molecules, functions as a long-range morphogen in patterning of the embryo and the adult appendages. Dpp signals via the SMAD proteins Mad and Medea. Here we show that in the absence of brinker (brk), Mad is not required for the activation of Dpp target genes that depend on low levels of Dpp. brk encodes a novel protein with features of a transcriptional repressor. brk itself is negatively regulated by Dpp. Dpp signaling might relieve brk's repression of low-level target genes either by transcriptional repression of brk or by antagonizing a repressor function of brk at the target gene promoters.

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

“…In the wing and leg imaginal discs, brk expression is repressed by and is roughly reciprocal to Dpp signaling. Hence, in the leg disc, brk expression is lowest in dorsal-most leg cells (Jazwinska et al, 1999;Muller et al, 2003) (Fig. 6B).…”

“…The following fly strains were used in this study: smo IIG26 FRT40A/CyO (Blair and Ralston, 1997), dpp d6 /CyO, dpp d12 /CyO (Spencer et al, 1982), w; wg Sp-1 /CyO; dpp blk -Gal4 /TM6B, Tb1 (Staehling-Hampton et al, 1994), y w brk 38-3 f 36a FRT18A/FM7 (Minami et al, 1999), UAS-brk, brk-lacZ (Jazwinska et al, 1999), UAS-tkv Q253D (Nellen et al, 1996) and D-h-lacZ (Hays et al, 1999). smo IIG26 is a strong hypomorphic mutation (van den Heuvel and Ingham, 1996).…”

“…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.…”

“…It appears that in legs overexpressing brk, there are fewer HHRE-GFP and D-h-CB-GFPexpressing cells. This is probably due to compromised growth of leg discs when Brk levels are elevated near the AP boundary (Jazwinska et al, 1999). transgenes.…”

“…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.…”