Department of Mathematical Sciences, Georgia Southern University Statesboro, GA, United States.
Department of Mathematical Sciences, Georgia Southern University Statesboro, GA, United States.
Math Biosci. 2019 Aug;314:13-27. doi: 10.1016/j.mbs.2019.05.001. Epub 2019 May 11.
The wing imaginal disc of Drosophila is one of the commonly used model systems for the studies of patterning, growth, and scaling. Development of the wing disc involves many interacting components as well as a variety of compound processes whose underlying mechanisms are still under investigation. For instance, it remains unclear about how to form compound experimentally-measured patterns of Decapentaplegic (Dpp) type-I receptor Thickveins (Tkv), as well as phosphorylated Mothers Against Dpp (pMad, the latter of which is the indicator of Dpp signaling activities. In this work, we proposed a baseline mathematical model that integrates established experimental facts to investigate the formation of pMad and Tkv gradients. Our model is validated by the accurate reproduction of complex asymmetric profiles of Tkv and pMad in both anterior and posterior compartments of the wing disc. Moreover, using our model as a numerical platform, we examined specific roles played by Engrailed (En), Hedgehog (Hh) and Dpp in the establishment of Tkv and pMad profiles. It turns out that En, Hh, Dpp all play an essential role in the formation of pMad and Tkv patterns. In particular, our proposed model supports the crucial part of the downregulation of Tkv by Dpp. Further, dual negative regulations of Tkv by both Hh and Dpp simultaneously prevent the Dpp signaling from interfering the Hh signaling and expand the effective range of Dpp gradients. Finally, parameter sensitivity was carried out to ensure that our results and conclusions are robust against specific choices of parameter values.
果蝇的翅盘是用于研究模式形成、生长和比例的常用模型系统之一。翅盘的发育涉及许多相互作用的成分以及各种复杂的过程,其潜在机制仍在研究中。例如,如何形成实验测量的 Decapentaplegic (Dpp) 型-I 受体 Thickveins (Tkv) 的复合模式,以及磷酸化 Mothers Against Dpp (pMad,后者是 Dpp 信号活动的指示剂,仍然不清楚。在这项工作中,我们提出了一个基本的数学模型,该模型整合了已建立的实验事实,以研究 pMad 和 Tkv 梯度的形成。我们的模型通过准确再现 wing disc 前、后区 Tkv 和 pMad 的复杂不对称轮廓来验证。此外,我们使用模型作为数值平台,研究了 Engrailed (En)、Hedgehog (Hh) 和 Dpp 在 Tkv 和 pMad 轮廓建立中的特定作用。事实证明,En、Hh、Dpp 都在 pMad 和 Tkv 模式的形成中起着重要作用。特别是,我们提出的模型支持 Dpp 下调 Tkv 的关键作用。此外,Hh 和 Dpp 对 Tkv 的双重负调控同时防止 Dpp 信号干扰 Hh 信号,并扩大 Dpp 梯度的有效范围。最后,进行了参数敏感性分析,以确保我们的结果和结论对参数值的特定选择具有稳健性。