PT  - JOURNAL ARTICLE
AU  - Yilun Zhu
AU  - Yuchi Qiu
AU  - Weitao Chen
AU  - Qing Nie
AU  - Arthur D. Lander
TI  - Feedback control of morphogen gradient scale
AID  - 10.1101/824292
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 824292
4099  - http://biorxiv.org/content/early/2019/10/31/824292.short
4100  - http://biorxiv.org/content/early/2019/10/31/824292.full
AB  - Gradients of the morphogen 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, we show here that Pent lacks a property essential to that model—the ability to spread with minimal loss throughout the morphogen field. Instead, Pent’s actions appear confined to within a few cell diameters of its site of synthesis, and can be phenocopied by manipulating non-diffusible targets of Pent strictly within the Pent expression domain. Through genetic manipulation 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 limit beyond which scaling fails—something we observe directly in wing discs.