论文标题
通过集成实验和理论模型，了解由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
论文作者
论文摘要
Notch信号传导是一种进化保守的细胞通信途径。除了调节单个细胞水平的细胞污染决策外，Notch信号传导还通过在胚胎发育，血管生成或伤口愈合中看到的，还通过配体 - 跨膜分子之间的配体 - 触发器相互作用来协调组织中新兴的时空图案。由于其无处不在的性质，Notch信号传导也与癌症进展的几个方面有关，包括肿瘤血管生成，癌细胞的干性和细胞浸润。在这里，我们回顾了实验和计算模型，以帮助了解Notch信号驱动的细胞模式的工作原理。首先，我们通过规范横向抑制和侧向诱导机制讨论空间图案的基本机制，包括血管生成，内耳发育和癌症转移的例子。接下来，我们分析了缺口途径中的其他复杂性层，例如各种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的可变结合亲和力。最后，我们讨论了在驱动集体上皮细胞迁移和心血管形态发生方面的凹槽途径中机械敏感性的最新证据。
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 to 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 such as the effects 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.
