The mechanosensitive channel Piezo1 cooperates with semaphorins to control neural crest migration.

The mechanosensitive channel Piezo1 cooperates with semaphorins to control neural crest migration.
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DOI:
10.1242/dev.200001
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发表时间:
2021-12-01
期刊:
Development (Cambridge, England)
影响因子:
--
通讯作者:
Mayor R
Mayor R
中科院分区:
其他
文献类型:
--
作者:
Canales Coutiño B;Mayor R

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细胞永久暴露于多种不同类型的信号:然而,细胞如何在复杂的体内环境中对同时发生的细胞外信号做出反应却知之甚少。在这里,我们研究了机械敏感离子通道Piezo1对神经嵴迁移的作用,这是一种多能胚胎细胞群。我们确定,Piezo1所需的爪蟾头神经嵴的迁移。我们发现,Piezo1的损失促进局灶性粘附周转和细胞骨架动力学控制Rac1活性,导致迁移速度加快。此外,由于Piezo1抑制,Rac 1的过度激活抵消了脑信号蛋白3A和脑信号蛋白3F的细胞迁移抑制信号,在体内产生异常的神经嵴侵入。因此,我们发现,在体内定向迁移,神经嵴细胞需要严格的调控Rac 1,由semaphorins和Piezo1。我们在这里揭示了通过Rac1的无数信号之间的平衡决定了体内细胞迁移,这是一种可能在其他细胞迁移过程中保守的机制。总结:神经嵴在体内的定向和正常迁移需要分别通过Semaphorin 3A和Piezo1对Rac 1进行化学和机械调节。
Cells are permanently exposed to a multitude of different kinds of signals: however, how cells respond to simultaneous extracellular signals within a complex in vivo environment is poorly understood. Here, we studied the role of the mechanosensitive ion channel Piezo1 on the migration of the neural crest, a multipotent embryonic cell population. We identify that Piezo1 is required for the migration of Xenopus cephalic neural crest. We show that loss of Piezo1 promotes focal adhesion turnover and cytoskeletal dynamics by controlling Rac1 activity, leading to increased speed of migration. Moreover, overactivation of Rac1, due to Piezo1 inhibition, counteracts cell migration inhibitory signals by Semaphorin 3A and Semaphorin 3F, generating aberrant neural crest invasion in vivo. Thus, we find that, for directional migration in vivo, neural crest cells require a tight regulation of Rac1, by semaphorins and Piezo1. We reveal here that a balance between a myriad of signals through Rac1 dictates cell migration in vivo, a mechanism that is likely to be conserved in other cell migration processes. Summary: Neural crest directional and normal migration in vivo requires both chemical and mechanical regulation of Rac1 by Semaphorin 3A and Piezo1, respectively.
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