论文标题

建模具有混合信号传导机制的双层组织中极性驱动的层流图案

Modelling polarity-driven laminar patterns in bilayer tissues with mixed signalling mechanisms

论文作者

Moore, Joshua W., Dale, Trevor C., Woolley, Thomas E.

论文摘要

高分辨率实验方法的最新进展突出了细胞信号途径串扰和局部信号传导在众多生物系统的发育和疾病中的重要性。对多个信号途径的研究通常会引入不同的细胞传输方法,即基于接触的或扩散信号,从而产生了对细胞行为的空间和时间依赖性。由控制双层组织中的细胞效果决策的细胞机制,我们使用动力学系统,再加上多层图来分析信号传导极性和途径串扰在细粒度形成蛋白质活性中的作用。具体而言,我们研究了多层图边缘结构和权重如何影响双层结构中细胞的层(层层)模式,这通常是在腺体组织中发现的。我们呈现出足够的条件,在大规模离散的动力系统中存在均匀细胞状态的存在,独特性和不稳定性。通过图形分配方法使用模式模板的方法来生成商系统与单调动力学系统的概念结合使用,我们利用了广泛的维度降低,以提供诱导多个空间依赖性细胞内成分的细粒层状模式所需的极性条件。然后,我们探索商和大规模动力学系统之间的光谱联系,以扩展层状图案标准从存在到收敛性,以在大型动力系统中足够大量的细胞极性,与组织中的空间尺寸和细胞数量无关。

Recent advances in high-resolution experimental methods have highlighted the significance of cell signal pathway crosstalk and localised signalling activity in the development and disease of numerous biological systems. The investigation of multiple signal pathways often introduces different methods of cell-cell communication, i.e. contact-based or diffusive signalling, which generates both a spatial and temporal dependence on cell behaviours. Motivated by cellular mechanisms that control cell-fate decisions in developing bilayer tissues, we use dynamical systems coupled with multilayer graphs to analyse the role of signalling polarity and pathway crosstalk in fine-grain pattern formation of protein activity. Specifically, we study how multilayer graph edge structures and weights influence the layer-wise (laminar) patterning of cells in bilayer structures, which are commonly found in glandular tissues. We present sufficient conditions for existence, uniqueness and instability of homogeneous cell states in the large-scale spatially discrete dynamical system. Using methods of pattern templating by graph partitioning to generate quotient systems in combination with concepts from monotone dynamical systems, we exploit the extensive dimensionality reduction to provide existence conditions for the polarity required to induce fine-grain laminar patterns with multiple spatially dependent intracellular components. We then explore the spectral links between the quotient and large-scale dynamical systems to extend the laminar patterning criteria from existence to convergence for sufficiently large amounts of cellular polarity in the large-scale dynamical system, independent of spatial dimension and number of cells in the tissue.

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