Randall Centre for Cell and Molecular Biophysics, Guy's Campus, King's College London, London, United Kingdom.
Cellular Adaptive Behaviour Lab, Francis Crick Institute, London, United Kingdom.
Elife. 2022 Apr 19;11:e73550. doi: 10.7554/eLife.73550.
Coordination of cell proliferation and migration is fundamental for life, and its dysregulation has catastrophic consequences, such as cancer. How cell cycle progression affects migration, and vice versa, remains largely unknown. We address these questions by combining in silico modelling and in vivo experimentation in the zebrafish trunk neural crest (TNC). TNC migrate collectively, forming chains with a leader cell directing the movement of trailing followers. We show that the acquisition of migratory identity is autonomously controlled by Notch signalling in TNC. High Notch activity defines leaders, while low Notch determines followers. Moreover, cell cycle progression is required for TNC migration and is regulated by Notch. Cells with low Notch activity stay longer in G and become followers, while leaders with high Notch activity quickly undergo G/S transition and remain in S-phase longer. In conclusion, TNC migratory identities are defined through the interaction of Notch signalling and cell cycle progression.
细胞增殖和迁移的协调是生命的基础，其失调会产生灾难性的后果，如癌症。细胞周期进程如何影响迁移，反之亦然，在很大程度上仍不清楚。我们通过在斑马鱼躯干神经嵴（TNC）中结合计算机模拟和体内实验来解决这些问题。TNC 集体迁移，形成带有一个领导细胞的链，该细胞引导后续跟随细胞的运动。我们表明，TNC 中 Notch 信号的自主控制决定了迁移身份的获得。高 Notch 活性定义了领导者，而低 Notch 活性则决定了跟随者。此外，细胞周期进程是 TNC 迁移所必需的，并受 Notch 调节。低 Notch 活性的细胞在 G 期停留时间更长，成为跟随者，而高 Notch 活性的领导者则迅速经历 G1/S 转换，并在 S 期停留更长时间。总之，TNC 的迁移身份是通过 Notch 信号和细胞周期进程的相互作用来定义的。
