Scaling a Dpp Morphogen Gradient through Feedback Control of Receptors and Co-receptors

• Published in: Developmental cell 2020-06, Vol.53 (6), p.724-739.e14
• Main Authors: Zhu, Yilun, Qiu, Yuchi, Chen, Weitao, Nie, Qing, Lander, Arthur D.
• Format: Article
• Language: English
• Subjects: Animals; decapentaplegic; Down-Regulation; Drosophila; Drosophila melanogaster; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - metabolism; feedback control; Feedback, Physiological; Gene Expression Regulation, Developmental; growth control; heparan sulfate proteoglycan; Imaginal Discs - embryology; Imaginal Discs - metabolism; mathematical modeling; Models, Theoretical; Morphogenesis; pattern formation; pentagone; scaling; wing disc
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2020.05.029

Gradients of decapentaplegic (Dpp) pattern Drosophila wing imaginal discs, establishing gene expression boundaries at specific locations. As discs grow, Dpp gradients expand, keeping relative boundary positions approximately stationary. Such scaling fails in mutants for Pentagone (pent), a gene repressed by Dpp that encodes a diffusible protein that expands Dpp gradients. Although these properties fit a recent mathematical model of automatic gradient scaling, that model requires an expander that spreads with minimal loss throughout a morphogen field. Here, we show that Pent’s actions are confined to within just a few cell diameters of its site of synthesis and can be phenocopied by manipulating non-diffusible Pent targets strictly within the Pent expression domain. Using genetics and mathematical modeling, we develop an alternative model of scaling driven by feedback downregulation of Dpp receptors and co-receptors. Among the model’s predictions is a size beyond which scaling fails—something we observe directly in wing discs. [Display omitted] •The Dpp morphogen gradient of the Drosophila wing disc scales with disc size•Feedback downregulation of receptors and co-receptors is required for gradient scaling•A mathematical model shows how moving boundaries, growth, and feedback work together•The secreted expander Pentagone does not spread sufficiently to explain scaling Zhu et al. investigate how a morphogen gradient expands to fit a growing domain. They argue that initial boundary conditions, tissue growth, and feedback downregulation of receptor and co-receptor expression together create a positional information system that scales automatically, yet transiently.