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通过整合实验与理论模型理解Notch信号驱动的模式形成原理

Understanding the Principles of Pattern Formation Driven by Notch Signaling by Integrating Experiments and Theoretical Models.

作者信息

Bocci Federico, Onuchic José Nelson, Jolly Mohit Kumar

机构信息

Center for Theoretical Biological Physics, Rice University, Houston, TX, United States.

Department of Physics and Astronomy, Rice University, Houston, TX, United States.

出版信息

Front Physiol. 2020 Jul 31;11:929. doi: 10.3389/fphys.2020.00929. eCollection 2020.

DOI:10.3389/fphys.2020.00929
PMID:32848867
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7411240/
Abstract

Notch signaling is an evolutionary conserved cell-cell communication pathway. Besides regulating cell-fate decisions at an individual cell level, Notch signaling coordinates the emergent spatiotemporal patterning in a tissue through ligand-receptor interactions among transmembrane molecules of neighboring cells, as seen in embryonic development, angiogenesis, or wound healing. Due to its ubiquitous nature, Notch signaling is also implicated in several aspects of cancer progression, including tumor angiogenesis, stemness of cancer cells and cellular invasion. Here, we review experimental and computational models that help understand the operating principles of cell patterning driven by Notch signaling. First, we discuss the basic mechanisms of spatial patterning via canonical lateral inhibition and lateral induction mechanisms, including examples from angiogenesis, inner ear development and cancer metastasis. Next, we analyze additional layers of complexity in the Notch pathway, including the effect of varying cell sizes and shapes, ligand-receptor binding within the same cell, variable binding affinity of different ligand/receptor subtypes, and filopodia. Finally, we discuss some recent evidence of mechanosensitivity in the Notch pathway in driving collective epithelial cell migration and cardiovascular morphogenesis.

摘要

Notch信号通路是一种进化保守的细胞间通讯途径。除了在单个细胞水平上调节细胞命运决定外，Notch信号通路还通过相邻细胞跨膜分子之间的配体-受体相互作用，协调组织中出现的时空模式，如在胚胎发育、血管生成或伤口愈合中所见。由于其普遍存在的性质，Notch信号通路也与癌症进展的几个方面有关，包括肿瘤血管生成、癌细胞干性和细胞侵袭。在这里，我们综述了有助于理解由Notch信号通路驱动的细胞模式运作原理的实验和计算模型。首先，我们讨论通过经典侧向抑制和侧向诱导机制进行空间模式形成的基本机制，包括来自血管生成、内耳发育和癌症转移的例子。接下来，我们分析Notch通路中额外的复杂层面，包括不同细胞大小和形状的影响、同一细胞内的配体-受体结合、不同配体/受体亚型的可变结合亲和力以及丝状伪足。最后，我们讨论Notch通路中机械敏感性在驱动集体上皮细胞迁移和心血管形态发生方面的一些最新证据。

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