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果蝇翅盘前后模式形成 I:一个基本的数学模型。

Anterior-posterior patterning of Drosophila wing discs I: A baseline mathematical model.

机构信息

Department of Mathematical Sciences, Georgia Southern University Statesboro, GA, United States.

Department of Mathematical Sciences, Georgia Southern University Statesboro, GA, United States.

出版信息

Math Biosci. 2019 Aug;314:13-27. doi: 10.1016/j.mbs.2019.05.001. Epub 2019 May 11.

DOI:10.1016/j.mbs.2019.05.001
PMID:31085191
Abstract

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.

摘要

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。

相似文献

1
Anterior-posterior patterning of Drosophila wing discs I: A baseline mathematical model.果蝇翅盘前后模式形成 I:一个基本的数学模型。
Math Biosci. 2019 Aug;314:13-27. doi: 10.1016/j.mbs.2019.05.001. Epub 2019 May 11.
2
The formation of the Thickveins (Tkv) gradient in Drosophila wing discs: A theoretical study.果蝇翅盘中 Thickveins(Tkv)梯度的形成:理论研究。
J Theor Biol. 2019 Aug 7;474:25-41. doi: 10.1016/j.jtbi.2019.04.015. Epub 2019 Apr 15.
3
Robustness of the Dpp morphogen activity gradient depends on negative feedback regulation by the inhibitory Smad, Dad.Dpp 形态发生素活性梯度的稳健性取决于抑制性 Smad 蛋白 Dad 的负反馈调节。
Dev Growth Differ. 2011 Jun;53(5):668-78. doi: 10.1111/j.1440-169X.2011.01274.x.
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Logical modelling of the role of the Hh pathway in the patterning of the Drosophila wing disc.Hh信号通路在果蝇翅盘模式形成中作用的逻辑建模。
Bioinformatics. 2008 Aug 15;24(16):i234-40. doi: 10.1093/bioinformatics/btn266.
5
Hedgehog creates a gradient of DPP activity in Drosophila wing imaginal discs.刺猬蛋白在果蝇翅成虫盘内形成了一种梯度的DPP活性。
Mol Cell. 2000 Jan;5(1):59-71. doi: 10.1016/s1097-2765(00)80403-7.
6
Dual function of the Drosophila Alk1/Alk2 ortholog Saxophone shapes the Bmp activity gradient in the wing imaginal disc.果蝇Alk1/Alk2直系同源基因萨克斯风的双重功能塑造了翅成虫盘的骨形态发生蛋白活性梯度。
Development. 2006 Sep;133(17):3295-303. doi: 10.1242/dev.02513. Epub 2006 Aug 3.
7
Asymmetric requirement of Dpp/BMP morphogen dispersal in the Drosophila wing disc.果蝇翅膀中 Dpp/BMP 形态发生素弥散的非对称需求。
Nat Commun. 2021 Nov 8;12(1):6435. doi: 10.1038/s41467-021-26726-6.
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Connecting Hh, Dpp and EGF signalling in patterning of the Drosophila wing; the pivotal role of collier/knot in the AP organiser.在果蝇翅膀模式形成中连接Hh、Dpp和EGF信号通路;collier/knot在前后轴组织者中的关键作用。
Development. 2002 Sep;129(18):4261-9. doi: 10.1242/dev.129.18.4261.
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mtv shapes the activity gradient of the Dpp morphogen through regulation of thickveins.mtv通过调控粗脉来塑造Dpp形态发生素的活性梯度。
Development. 2001 Jan;128(1):67-74. doi: 10.1242/dev.128.1.67.
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Signaling through both type I DPP receptors is required for anterior-posterior patterning of the entire Drosophila wing.果蝇整个翅膀的前后模式形成需要通过I型DPP受体进行信号传导。
Development. 1997 Jan;124(1):79-89. doi: 10.1242/dev.124.1.79.

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