Modeling the Notch Response.
Modeling the Notch Response.
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DOI：
10.1007/978-3-319-89512-3_5
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发表时间：
2018
影响因子：
--
通讯作者：
Sprinzak D
中科院分区：
文献类型：
--
作者：
Binshtok U;Sprinzak D
NOTCH信号调节动物王国中所有组织和所有生物体的发育过程。它通常参与协调相邻细胞分化为不同细胞类型。随着我们对NOTCH通路的结构、分子和细胞特性的了解不断扩大，更需要定量方法来更好地了解NOTCH信号转导控制的过程。近年来，NOTCH信号传导和NOTCH介导的模式化的理论和计算方法越来越受欢迎。NOTCH介导的模式化的数学模型提供了对复杂和违反直觉的行为的洞察，并且可以帮助生成可以指导实验的预测。在这一章中，我们回顾了NOTCH介导的模式化过程的最新进展。我们讨论了新的建模方法，侧抑制模式，考虑到顺式NOTCH受体和配体之间的相互作用，通过长细胞突起，细胞分裂过程中的信号，耦合到外部信号。我们还描述了模型的体节发生，其中NOTCH信号被用于同步细胞振荡。然后，我们讨论建模方法，考虑细胞形态对NOTCH信号和NOTCH介导的图案的影响。最后，我们考虑模型的边界形成，以及它们是如何受到多个配体的组合作用。这些主题涵盖了NOTCH响应建模领域的主要进展。
NOTCH signaling regulates developmental processes in all tissues and all organisms across the animal kingdom. It is often involved in coordinating the differentiation of neighboring cells into different cell types. As our knowledge on the structural, molecular and cellular properties of the NOTCH pathway expands, there is a greater need for quantitative methodologies to get a better understanding of the processes controlled by NOTCH signaling. In recent years, theoretical and computational approaches to NOTCH signaling and NOTCH mediated patterning are gaining popularity. Mathematical models of NOTCH mediated patterning provide insight into complex and counterintuitive behaviors and can help to generate predictions that can guide experiments. In this chapter, we review the recent advances in modeling NOTCH mediated patterning processes. We discuss new modeling approaches to lateral inhibition patterning that take into account cis-interactions between NOTCH receptors and ligands, signaling through long cellular protrusions, cell division processes, and coupling to external signals. We also describe models of somitogenesis, where NOTCH signaling is used for synchronizing cellular oscillations. We then discuss modeling approaches that consider the effect of cell morphology on NOTCH signaling and NOTCH mediated patterning. Finally, we consider models of boundary formation and how they are influenced by the combinatorial action of multiple ligands. Together, these topics cover the main advances in the field of modeling the NOTCH response.
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