通过整合实验和理论模型来理解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
摘要：
Notch信号转导是一种进化上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信号传导还通过相邻细胞的跨膜分子之间的配体-受体相互作用来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信号传导还涉及癌症进展的几个方面，包括肿瘤血管生成、癌细胞的干性和细胞侵袭。在这里，我们回顾了实验和计算模型，以帮助理解Notch信号驱动的细胞模式的工作原理。首先，我们讨论了通过典型的侧抑制和侧诱导机制，包括从血管生成，内耳发育和癌症转移的例子空间图案的基本机制。接下来，我们分析了Notch途径中的其他复杂层，例如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，我们讨论了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中的一些最新证据。
英文摘要：
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.
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