Control of Dpp morphogen signalling by a secreted feedback regulator

In many instances during development, morphogens specify cell fates by forming concentration gradients. In the Drosophila melanogaster wing imaginal disc, Decapentaplegic (Dpp), a bone morphogenetic protein (BMP), functions as a long-range morphogen to control patterning and growth(1). Dpp is secreted from a stripe of cells at the anterior-posterior compartment boundary and spreads into both compartments to generate a characteristic BMP activity gradient(2-6). Ever since the identification of the morphogen activity of Dpp in the developing wing, the system has served as a paradigm to understand how long-range gradients are established and how cells respond to such gradients. Here we reveal the tight and direct connection of these two processes with the identification and characterization of pentagone (pent), a transcriptional target of BMP signalling encoding a secreted regulator of the pathway. Absence of pent in the wing disc causes a severe contraction of the BMP activity gradient resulting in patterning and growth defects. We show that Pent interacts with the glypican Dally to control Dpp distribution and provide evidence that proper establishment of the BMP morphogen gradient requires the inbuilt feedback loop embodied by Pent.