Department of Mathematical Sciences, Georgia Southern University, Statesboro, GA, United States.
J Theor Biol. 2019 Aug 7;474:25-41. doi: 10.1016/j.jtbi.2019.04.015. Epub 2019 Apr 15.
The development of the wing imaginal disc (wing disc) is commonly adopted for the studies of patterning and growth which are two fundamental problems in developmental biology. Decapentaplegic (Dpp) signaling regulates several aspects of wing development, such as the anterior (A)-posterior (P) patterning, cellular growth rate, and cell adhesion. The distribution and activity of Dpp signaling are controlled in part by the expression level of its major type I receptor, Thickveins (Tkv). In this paper, we focus on theoretically investigating mechanisms by which the highly asymmetric pattern of Tkv is established in Drosophila wing discs. To the end, a mathematical model of Hh signaling and Dpp signaling is proposed and validated by comparisons with experimental observations. Our model provides a comprehensive view of the formation of Tkv gradients in wing discs. We found that engrailed (En), Hedgehog (Hh) signaling, and Dpp signaling cooperate to establish the asymmetric gradients of Tkv and pMad in the wing disc. Moreover, our model suggests a Brinker-mediated mechanism of Dpp-dependent repression of Tkv. Based on this mechanism, a couple of predicted experimental observations have been provided for further lab confirmation.
翅膀 imaginal 盘（wing disc）的发育通常被用于研究形态发生和生长，这是发育生物学中的两个基本问题。Decapentaplegic（Dpp）信号调节翅膀发育的几个方面，如前后（A-P）模式、细胞生长率和细胞黏附。Dpp 信号的分布和活性部分受到其主要类型 I 受体 Thickveins（Tkv）的表达水平的控制。在本文中，我们专注于从理论上研究在果蝇翅膀盘中建立 Tkv 高度不对称模式的机制。为此，提出并验证了一个关于 Hh 信号和 Dpp 信号的数学模型，通过与实验观察结果进行比较。我们的模型提供了一个全面的视角来看待翅膀盘中 Tkv 梯度的形成。我们发现，Engrailed（En）、Hedgehog（Hh）信号和 Dpp 信号合作，在翅膀盘中建立了 Tkv 和 pMad 的不对称梯度。此外，我们的模型提出了一个 Brink 介导的 Dpp 依赖性 Tkv 抑制机制。基于这个机制，我们提供了一些预测的实验观察结果，以供进一步的实验室确认。
