当前位置: X-MOL 学术Stud. Appl. Math. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Cell-Surface Bound Nonreceptors and Signaling Morphogen Gradients
Studies in Applied Mathematics ( IF 2.7 ) Pub Date : 2014-02-04 , DOI: 10.1111/sapm.12030
Frederic Y M Wan 1
Affiliation  

The patterning of many developing tissues is orchestrated by gradients of signaling morphogens. Included among the molecular events that drive the formation of morphogen gradients are a variety of elaborate regulatory interactions. Such interactions are thought to make gradients robust, i.e. insensitive to change in the face of genetic or environmental perturbations. But just how this is accomplished is a major unanswered question. Recently extensive numerical simulations suggest that robustness of signaling gradients can be achieved through morphogen degradation mediated by cell surface bound non-signaling receptor molecules (or nonreceptors for short) such as heparan sulfate proteoglycans (HSPG). The present paper provides a mathematical validation of the results from the aforementioned numerical experiments. Extension of a basic extracellular model to include reversible binding with nonreceptors synthesized at a prescribed rate and mediated morphogen degradation shows that the signaling gradient diminishes with increasing concentration of cell-surface nonreceptors. Perturbation and asymptotic solutions obtained for i) low (receptor and nonreceptor) occupancy, and ii) high nonreceptor concntration permit more explicit delineation of the effects of nonreceptors on signaling gradients and facilitate the identification of scenarios in which the presence of nonreceptors may or may not be effective in promoting robustness.

中文翻译:

细胞表面结合的非受体和信号形态原梯度

许多发育中的组织的模式是由信号形态发生素的梯度精心编排的。驱动形态发生素梯度形成的分子事件包括各种复杂的调控相互作用。这种相互作用被认为使梯度稳健,即在面对遗传或环境扰动时对变化不敏感。但是,这是如何实现的仍然是一个悬而未决的重大问题。最近广泛的数值模拟表明,信号梯度的稳健性可以通过细胞表面结合的非信号受体分子(或简称为非受体)如硫酸乙酰肝素蛋白聚糖 (HSPG) 介导的形态发生素降解来实现。本论文对上述数值实验的结果进行了数学验证。扩展基本细胞外模型以包括与以规定速率合成的非受体的可逆结合和介导的形态发生素降解表明信号梯度随着细胞表面非受体浓度的增加而减少。为 i) 低(受体和非受体)占用率和 ii) 高非受体浓度获得的扰动和渐近解允许更明确地描绘非受体对信号梯度的影响,并有助于识别非受体可能存在或不存在的场景有效促进稳健性。
更新日期:2014-02-04
down
wechat
bug