Establishment and maintenance of planar epithelial cell polarity by asymmetric cadherin bridges: A computer model
Establishment and maintenance of planar epithelial cell polarity by asymmetric cadherin bridges: A computer model
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DOI：
10.1002/dvdy.20617
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发表时间：
2006-01-01
影响因子：
2.5
通讯作者：
Kerszberg, M
中科院分区：
文献类型：
--
作者：
Le Garrec, JF;Lopez, P;Kerszberg, M
由于上皮平面上的细胞极化，动物的鳞片、毛、羽毛和纤毛是定向的。相关基因已经确定，但信号和机制仍不清楚。在果蝇的翅膀极化中，人们普遍认为Frizzleed活动的梯度作用；而由钙粘附素(如Flamingo)发出的细胞-细胞信号肯定起着重要作用。我们提出了一个计算机模型，其中通过偏向的、反馈强化的基于Flamingo的不对称细胞间复合体的形成来读取Frizzled梯度。通过这些复合体，邻近的细胞能够比较它们的Frizzleed活动水平。我们的计算具有很高的抗噪能力，可以再现野生型和所有已知的突变翼型；还可以预测其他表型。该模型对Frizzled型激活信号施加了严格的限制，它应该表现出不寻常的特性：(1)细胞外的Frizzled型信号梯度应该是反向递减的，从近端(P)到远端(D)，而在极化过程中，细胞内的Frizzled型梯度从P到D建立；(2)外部梯度应该相对较弱和短暂，以免防止细胞内Frizzled型信号的倒置。这些特征在很大程度上与模型细节无关，可能会为未来的实验工作提供有用的线索。
Animal scales, hairs, feathers, and cilia are oriented due to cell polarization in the epithelial plane. Genes involved have been identified, but the signal and mechanism remain unknown. In Drosophila wing polarization, the action of a gradient of Frizzled activity is widely assumed; and cell-cell signalling by cadherins such as Flamingo surely plays a major role. We present a computer model where reading the Frizzled gradient occurs through biased, feedback-reinforced formation of Flamingo-based asymmetric intercellular complexes. Through these complexes neighboring cells are able to compare their Frizzled activity levels. Our computations are highly noise-resistant and reproduce both wild-type and all known mutant wing phenotypes; other phenotypes are predicted. The model puts stringent limits on a Frizzled activation signal, which should exhibit unusual properties: (1) the extracellular Frizzled signalling gradient should be counterdirectional-decreasing from proximal (P) to distal (D), whereas during polarization, the intracellular Frizzled gradient builds up from P to D; (2) the external gradient should be relatively weak and short-lived, lest it prevent inversion of intracellular Frizzled. These features, largely independent of model details, may, provide useful clues for future experimental efforts.