Notch controls the cell cycle to define leader versus follower identities during collective cell migration.
Notch controls the cell cycle to define leader versus follower identities during collective cell migration.
复制标题
Notch控制了细胞周期，以定义集体细胞迁移期间的领导者与追随者身份。
DOI：
10.7554/elife.73550
复制
发表时间：
2022-04-19
期刊：
影响因子：
7.7
通讯作者：
Linker, Claudia
中科院分区：
文献类型：
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作者：
Alhashem, Zain;Feldner-Busztin, Dylan;Revell, Christopher;Portillo, Macarena Alvarez-Garcillan;Camargo-Sosa, Karen;Richardson, Joanna;Rocha, Manuel;Gauert, Anton;Corbeaux, Tatianna;Milanetto, Martina;Argenton, Francesco;Tiso, Natascia;Kelsh, Robert N.;Prince, Victoria E.;Bentley, Katie;Linker, Claudia
细胞增殖和迁移的协调是生命的基础，其失调具有灾难性的后果，如癌症。细胞周期进程如何影响迁移，反之亦然，仍然是未知的。我们解决这些问题相结合的模拟和在斑马鱼躯干神经嵴（TNC）的体内实验。跨国公司集体迁移，形成一个由领导者引导尾随者的连锁。我们发现，收购的迁移身份是自主控制的Notch信号在TNC。高Notch活动定义领导者，而低Notch活动定义追随者。此外，细胞周期进程是TNC迁移所必需的，并受Notch调节。具有低Notch活性的细胞在G1期停留更长时间并成为跟随者，而具有高Notch活性的领导者迅速经历G1/S转换并在S期停留更长时间。总之，TNC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。
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 G1 and become followers, while leaders with high Notch activity quickly undergo G1/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.