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极化分子分布的各向异性传播是平面细胞极化涡旋模式的常见机制吗?

Is anisotropic propagation of polarized molecular distribution the common mechanism of swirling patterns of planar cell polarization?

作者信息

Zhu Hao

机构信息

Division of Applied Mathematics, School of Mathematical Sciences, University of Nottingham, Nottingham NG7 2RD, UK.

出版信息

J Theor Biol. 2009 Feb 7;256(3):315-25. doi: 10.1016/j.jtbi.2008.08.029. Epub 2008 Sep 23.

Abstract

Mutations in multiple planar cell polarity (PCP) genes can cause swirling patterns indicated by whorls and tufts of hairs in the wings and the abdomen of Drosophila and in the skin of vertebrates. Damaged global directional cue caused by mutations in four-jointed, fat, and dachsous, impaired cellular hexagonal packing caused by mutations in frizzled, or weakened intracellular signaling caused by mutations in disheveled, inturned, and prickle all make hair patterns globally irregular yet locally aligned, and in some cases, typically swirling. Why and how mutations in different genes all lead to swirling patterns is unexplored. Although the mechanisms of molecular signaling remain unclear, the features of molecular distribution are evident-most PCP molecules develop the polarized distribution in cells and this distribution can be induced by intercellular signaling. Does this suggest something fundamental to swirling patterns beyond the particular functions of genes, proteins, and signaling? A simple model indeed indicates this. Disregarding detailed molecular interactions, the induced polarization of molecular distribution in an epithelial cell can be modeled as the induced polarization of positive and negative charge distribution in a dielectric molecule. Simulations reveal why and how mutations in different genes all lead to swirling patterns, and in particular, the conditions for generating typical swirling patterns. The results show that the anisotropic propagation of polarized molecular distribution may be the common mechanism of swirling patterns caused by different mutations. They also suggest that at the cell level, as at the molecular level, a simple mechanism can generate complex and diverse patterning phenotypes in different molecular contexts. The similarity between the induced polarization and its propagation in both the epithelial cells and the dielectric molecules also interestingly suggests some commonalities between pattern formation in the biological and physical systems.

摘要

多个平面细胞极性(PCP)基因的突变可导致果蝇翅膀和腹部以及脊椎动物皮肤中出现由毛发漩涡和簇状表示的漩涡图案。四关节、脂肪和 Dachsous 基因的突变导致全局方向线索受损,卷曲蛋白基因的突变导致细胞六边形堆积受损,或蓬乱、内翻和刺痛基因的突变导致细胞内信号减弱,所有这些都会使毛发图案在全局上不规则但在局部上对齐,并且在某些情况下通常呈漩涡状。不同基因的突变为何以及如何都导致漩涡图案尚不清楚。尽管分子信号传导机制仍不明确,但分子分布特征是明显的——大多数 PCP 分子在细胞中形成极化分布,并且这种分布可由细胞间信号传导诱导。这是否暗示了除基因、蛋白质和信号传导特定功能之外的漩涡图案的一些基本特征?一个简单的模型确实表明了这一点。忽略详细的分子相互作用,上皮细胞中分子分布的诱导极化可以建模为介电分子中正电荷和负电荷分布的诱导极化。模拟揭示了不同基因的突变为何以及如何都导致漩涡图案,特别是产生典型漩涡图案的条件。结果表明,极化分子分布的各向异性传播可能是不同突变导致漩涡图案的共同机制。它们还表明,在细胞水平上,如同在分子水平上一样,一个简单的机制可以在不同的分子背景下产生复杂多样的图案表型。上皮细胞和介电分子中诱导极化及其传播之间的相似性也有趣地暗示了生物系统和物理系统中图案形成之间的一些共性。

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