Mathematical modeling of planar cell polarity to understand domineering nonautonomy
Mathematical modeling of planar cell polarity to understand domineering nonautonomy
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DOI：
10.1126/science.1105471
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发表时间：
2005-01-21
期刊：
影响因子：
56.9
通讯作者：
Tomlin, CJ
中科院分区：
文献类型：
--
作者：
Amonlirdviman, K;Khare, NA;Tomlin, CJ
平面细胞极性 (PCP) 信号传导沿与上皮细胞[顶端-基底轴]正交的轴产生亚细胞不对称。通过一种知之甚少的机制，一些 PCP 信号成分（包括一些但不是全部受体卷曲等位基因）发生突变的细胞克隆会导致邻近野生型细胞的极性破坏，这种现象被称为霸道非自主性。在这里，通过反应扩散、偏微分方程建模和模拟，从实验结果中得出了接触依赖性信号假说，以完全重现果蝇翅膀中的 PCP 表型，包括霸道的非自主性。该模型的充分性和模型预测的实验验证揭示了特定的蛋白质-蛋白质相互作用如何产生自主性或专横的非自主性。
Planar cell polarity (PCP) signaling generates subcellular asymmetry along an axis orthogonal to the epithelia[ apical-basal axis. Through a poorly understood mechanism, cell clones that have mutations in some PCP signaling components, including some, but not all, alleles of the receptor frizzled, cause polarity disruptions of neighboring wild-type cells, a phenomenon referred to as domineering nonautonomy. Here, a contact-dependent signaling hypothesis, derived from experimental results, is shown by reaction-diffusion, partial differential equation modeling and simulation to fully reproduce PCP phenotypes, including domineering nonautonomy, in the Drosophila wing. The sufficiency of this model and the experimental validation of model predictions reveal how specific protein-protein interactions produce autonomy or domineering nonautonomy.