Scaling a Dpp morphogen gradient through feedback control of receptors and co-receptors. Zhu et al.

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 down-regulation 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. These data support a publication in Developmental Cell, June 22, 2020.果蝇翅成虫盘的发育由decapentaplegic（Dpp）浓度梯度调控，并在特定位置建立基因表达边界。随着翅成虫盘的生长，Dpp浓度梯度会同步扩展，使相对的基因表达边界位置大致保持稳定。Pentagone（pent）是一类受Dpp抑制的基因，其编码一种可扩散蛋白并能扩展Dpp浓度梯度；在该基因的突变体中，这种尺度缩放现象会失效。尽管上述特性符合近期提出的自动浓度梯度尺度缩放数学模型，但该模型要求存在一种可在形态发生场中以极小损耗扩散的扩展因子。本研究发现，Pent的作用范围仅局限于其合成位点周围数倍细胞直径的区域内；且仅在Pent的表达域内操控非可扩散性Pent靶标，即可实现表型模拟。本研究结合遗传学手段与数学建模，提出了一种由Dpp受体及其辅助受体的反馈下调所驱动的替代尺度缩放模型。该模型的核心预测之一是存在一个临界尺寸，当翅成虫盘超过该尺寸时尺度缩放将失效，这一现象我们已在果蝇翅成虫盘中直接观测到。本研究数据已被收录于2020年6月22日发表于《发育细胞》（Developmental Cell）的学术论文中。