Order and stochastic dynamics in Drosophila planar cell polarity.
Order and stochastic dynamics in Drosophila planar cell polarity.
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DOI：
10.1371/journal.pcbi.1000628
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发表时间：
2009-12
影响因子：
4.3
通讯作者：
Shraiman BI
中科院分区：
文献类型：
--
作者：
Burak Y;Shraiman BI
果蝇翅膀叶片中的细胞表现出平面内极化，导致毛发的远端取向。平面细胞极性(PCP)的建立涉及细胞间的相互作用以及全球定向信号。许多支持这一过程的遗传和分子成分已经被实验确定，最近一个先进的系统级模型表明，观察到的突变表型可以通过涉及膜结合蛋白不对称定位的细胞间相互作用来理解。在理解有序极化出现的关键开放问题中，随机性的影响和全球定向信号的作用。这些问题与我们对物理系统中铁磁性的理解密切相关。在这里，我们继续用这个类比来理解PCP秩序的出现。为此，我们发展了一个基本的分子过程的半唯象表示，并定义了一个模型的“相图”，它提供了表型对参数的依赖的全局视图。我们发现PCP的动力学过程有两个阶段：局域极化幅度的快速增长和从小到大的较慢的排列过程。我们讨论了组织对各种定向信号的响应，并表明在弱定向信号下可以实现全局PCP有序，只要它在过程的早期阶段起作用。最后，我们定义并讨论了该模型的一些实验预测。上皮组织的极化方向通常是偏向的，这决定了例如哺乳动物皮肤上毛发生长的方向、鱼的鳞片的方向、苍蝇眼的小眼排列和脊椎动物耳蜗的感觉毛细胞的排列。这种面内极化，称为平面细胞极性，是在发育过程中对组织构图起作用的形态发生场之一。在这里，我们关注苍蝇翅膀中的平面细胞极性，其中蛋白质定位和细胞间配体-受体相互作用与未知的定向信号相结合，建立了翅膀上皮的平面细胞极性。我们用统计力学的工具证明了这一过程与已被广泛研究的物理系统中的铁磁性模型之间的相似之处。这个类比有助于理解细胞之间的局部相互作用如何导致全局极化秩序，并阐明全局定向信号的作用和过程动力学对参数的依赖。我们证明，在没有外部定向信号的情况下，由于随机噪声，应该出现漩涡图案。我们提出了检验这一预测的方法，以及量化未知外部定向信号的幅度和空间变化的方法。
Cells in the wing blade of Drosophila melanogaster exhibit an in-plane polarization causing distal orientation of hairs. Establishment of the Planar Cell Polarity (PCP) involves intercellular interactions as well as a global orienting signal. Many of the genetic and molecular components underlying this process have been experimentally identified and a recently advanced system-level model has suggested that the observed mutant phenotypes can be understood in terms of intercellular interactions involving asymmetric localization of membrane bound proteins. Among key open questions in understanding the emergence of ordered polarization is the effect of stochasticity and the role of the global orienting signal. These issues relate closely to our understanding of ferromagnetism in physical systems. Here we pursue this analogy to understand the emergence of PCP order. To this end we develop a semi-phenomenological representation of the underlying molecular processes and define a “phase diagram” of the model which provides a global view of the dependence of the phenotype on parameters. We show that the dynamics of PCP has two regimes: rapid growth in the amplitude of local polarization followed by a slower process of alignment which progresses from small to large scales. We discuss the response of the tissue to various types of orienting signals and show that global PCP order can be achieved with a weak orienting signal provided that it acts during the early phase of the process. Finally we define and discuss some of the experimental predictions of the model. Epithelial tissues are often polarized in a preferred direction which determines, for example, the direction of hair growth on mammalian skin, the orientation of scales in fish, the alignment of ommatidia in the fly eye and of sensory hair cells in the vertebrate cochlea. This in-plane polarization, known as planar cell polarity, is one of the morphogenetic fields that play a role in tissue patterning during development. Here we focus on planar cell polarity in the fly wing, where protein localization and inter-cellular ligand-receptor interactions combine with an unknown orienting signal to establish planar cell polarity of the wing epithelium. We demonstrate an analogy between this process and models of ferromagnetism in physical systems that have been studied extensively using the tools of statistical mechanics. The analogy helps in understanding how local interactions between cells can lead to global polarization order and elucidate the role of global orienting signals and the dependence of the dynamics of the process on parameters. We demonstrate that in the absence of an external orienting signal swirling patterns should emerge due to random noise. We propose ways to test this prediction and ways to quantify the magnitude and spatial variation of the unknown external orienting signal.
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21.3
作者：
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