Modeling the morphodynamic galectin patterning network of the developing avian limb skeleton
Modeling the morphodynamic galectin patterning network of the developing avian limb skeleton
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DOI：
10.1016/j.jtbi.2013.12.004
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发表时间：
2014-04-07
影响因子：
2
通讯作者：
Newman, S. A.
中科院分区：
文献类型：
--
作者：
Glimm, T.;Bhat, R.;Newman, S. A.
我们提出了一个数学模型的形态发生和模式的间充质凝聚，作为原始的鸟类肢体骨骼。该模型基于实验建立的多尺度调节网络的动力学，该网络由两种在肢体发育早期表达的聚糖结合蛋白组成：CG（鸡凝集素）-1A、CG-8及其反受体，它们决定“原凝聚物”的形成、大小、数量和间距，这些“原凝聚物”引起凝聚，随后形成作为骨骼模板的软骨元素。该模型是一个偏微分和积分微分方程系统，其中包含一个通量项来表示局部粘附梯度，并以“完整”和“简化”形式进行模拟，以确认系统具有模式形成能力并探索模式不稳定性的本质。完整的模型定性和定量地总结了网络扰动的实验结果，并得出了新的预测，这些预测通过进一步的实验得到了验证。简化模型用于证明模式过程是固有的形态动力学，细胞运动是其固有的。此外，细胞运动和形态因子之间的正、负相互作用之间的微妙关系产生了规则的模式，而不需要具有广泛分散扩散系数的激活剂和抑制剂。因此，所描述的机制代表了激活剂-抑制剂过程类别的扩展，该过程能够产生具有重复元素的生物模式，超出了图灵/Gierer-Meinhardt类型的形态静止机制。(C) 2013 Elsevier Ltd.版权所有。
We present a mathematical model for the morphogenesis and patterning of the mesenchymal condensations that serve as primordia of the avian limb skeleton. The model is based on the experimentally established dynamics of a multiscale regulatory network consisting of two glycan-binding proteins expressed early in limb development: CG (chicken galectin)-1A, CG-8 and their counterreceptors that determine the formation, size, number and spacing of the "protocondensations" that give rise to the condensations and subsequently the cartilaginous elements that serve as the templates of the bones. The model, a system of partial differential and integro-differential equations containing a flux term to represent local adhesion gradients, is simulated in a "full" and a "reduced" form to confirm that the system has pattern-forming capabilities and to explore the nature of the patterning instability. The full model recapitulates qualitatively and quantitatively the experimental results of network perturbation and leads to new predictions, which are verified by further experimentation. The reduced model is used to demonstrate that the patteming process is inherently morphodynamic, with cell motility being intrinsic to it Furthermore, subtle relationships between cell movement and the positive and negative interactions between the morphogens produce regular patterns without the requirement for activators and inhibitors with widely separated diffusion coefficients. The described mechanism thus represents an extension of the category of activator-inhibitor processes capable of generating biological patterns with repetitive elements beyond the morphostatic mechanisms of the Turing/Gierer-Meinhardt type. (C) 2013 Elsevier Ltd. All rights reserved.