Control of osteoblast regeneration by a train of Erk activity waves.
Control of osteoblast regeneration by a train of Erk activity waves.
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一系列ERK活性波对成骨细胞再生的调控。
DOI：
10.1038/s41586-020-03085-8
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发表时间：
2021-03
期刊：
影响因子：
64.8
通讯作者：
Di Talia S
中科院分区：
文献类型：
--
作者：
De Simone A;Evanitsky MN;Hayden L;Cox BD;Wang J;Tornini VA;Ou J;Chao A;Poss KD;Di Talia S
再生是一个复杂的事件链，将组织恢复到其原始大小和形状。适当形态发生所需的细胞动力学的组织范围的协调受到再生身体部位的大尺寸的挑战。生化途径中的反馈机制可以提供远距离的有效沟通，但它们如何在组织再生过程中调节生长尚未解决。在这里，我们报告说，Erk活动的节奏行波控制再生斑马鱼鳞片，毫米大小的保护性身体盔甲盘的时间和空间的骨骼生长。我们发现Erk活动波以扩展的同心环的形式传播，从中央源广播，诱导成骨细胞组织生长的环状模式。使用理论和实验分析相结合，我们表明，Erk活动传播的可激发的触发波能够穿越整个规模在大约两天，与波生成的频率控制的规模再生的速度。此外，周期性诱导同步的、组织范围的Erk激活代替行波损害组织生长，表明波分布的Erk激活是再生的关键。我们的研究结果揭示了触发波作为协调细胞行为和指导再生过程中组织形态的调节策略。
Regeneration is a complex chain of events that restores a tissue to its original size and shape. The tissue-wide coordination of cellular dynamics needed for proper morphogenesis is challenged by the large dimensions of regenerating body parts. Feedback mechanisms in biochemical pathways can provide effective communication across great distances, but how they might regulate growth during tissue regeneration is unresolved. Here, we report that rhythmic traveling waves of Erk activity control the growth of bone in time and space in regenerating zebrafish scales, millimetre-sized discs of protective body armour. We find that Erk activity waves travel as expanding concentric rings, broadcast from a central source, inducing ring-like patterns of osteoblast tissue growth. Using a combination of theoretical and experimental analyses, we show that Erk activity propagates as excitable trigger waves able to traverse the entire scale in approximately two days, with the frequency of wave generation controlling the rate of scale regeneration. Furthermore, periodic induction of synchronous, tissue-wide Erk activation in place of travelling waves impairs tissue growth, indicating that wave-distributed Erk activation is key to regeneration. Our findings reveal trigger waves as a regulatory strategy to coordinate cell behaviour and instruct tissue form during regeneration.
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