Department of Cell and Developmental Biology, University College London, London, UK.
Nature. 2021 Dec;600(7890):690-694. doi: 10.1038/s41586-021-04210-x. Epub 2021 Dec 8.
Collective cell migration underlies morphogenesis, wound healing and cancer invasion. Most directed migration in vivo has been attributed to chemotaxis, whereby cells follow a chemical gradient. Cells can also follow a stiffness gradient in vitro, a process called durotaxis, but evidence for durotaxis in vivo is lacking. Here we show that in Xenopus laevis the neural crest-an embryonic cell population-self-generates a stiffness gradient in the adjacent placodal tissue, and follows this gradient by durotaxis. The gradient moves with the neural crest, which is continually pursuing a retreating region of high substrate stiffness. Mechanistically, the neural crest induces the gradient due to N-cadherin interactions with the placodes and senses the gradient through cell-matrix adhesions, resulting in polarized Rac activity and actomyosin contractility, which coordinates durotaxis. Durotaxis synergizes with chemotaxis, cooperatively polarizing actomyosin machinery of the cell group to prompt efficient directional collective cell migration in vivo. These results show that durotaxis and dynamic stiffness gradients exist in vivo, and gradients of chemical and mechanical signals cooperate to achieve efficient directional cell migration.
细胞集体迁移是形态发生、伤口愈合和癌症侵袭的基础。体内大多数定向迁移归因于趋化性，即细胞沿着化学梯度运动。细胞在体外也可以沿着刚度梯度运动，这一过程称为趋硬性，但是体内趋硬性的证据尚缺乏。在这里，我们发现在非洲爪蟾中，神经嵴——一种胚胎细胞群体——在相邻的基板组织中自发产生刚度梯度，并通过趋硬性沿着梯度运动。梯度随着神经嵴移动，神经嵴一直在追踪高基质刚度的退缩区域。从机制上讲，由于 N-钙黏蛋白与基板的相互作用，神经嵴诱导了梯度，并且通过细胞基质黏附来感知梯度，从而导致极化 Rac 活性和肌动球蛋白收缩性，协调趋硬性。趋硬性与趋化性协同作用，共同极化细胞群体的肌动球蛋白机械装置，从而在体内促进有效的定向集体细胞迁移。这些结果表明，趋硬性和动态刚度梯度存在于体内，并且化学和机械信号的梯度协同作用以实现有效的定向细胞迁移。
