1Department of Biological Sciences, Graduate School of Science, Osaka University, Suita, Osaka, 565-0871 Japan.
RIKEN Center for Biosystems Dynamics Research (BDR), Suita, Osaka, 565-0874 Japan.
Commun Biol. 2019 Jan 24;2:34. doi: 10.1038/s42003-018-0273-6. eCollection 2019.
In , a model organism for the study of collective cell migration, extracellular cyclic adenosine 3',5'-monophosphate (cAMP) acts as a diffusible chemical guidance cue for cell aggregation, which has been thought to be important in multicellular morphogenesis. Here we revealed that the dynamics of cAMP-mediated signaling showed a transition from propagating waves to steady state during cell development. Live-cell imaging of cytosolic cAMP levels revealed that their oscillation and propagation in cell populations were obvious for cell aggregation and mound formation stages, but they gradually disappeared when multicellular slugs started to migrate. A similar transition of signaling dynamics occurred with phosphatidylinositol 3,4,5-trisphosphate signaling, which is upstream of the cAMP signal pathway. This transition was programmed with concomitant developmental progression. We propose a new model in which cAMP oscillation and propagation between cells, which are important at the unicellular stage, are unessential for collective cell migration at the multicellular stage.
在 ，一种用于研究细胞集体迁移的模式生物，细胞外环腺苷酸 3'，5'-单磷酸（cAMP）作为细胞聚集的可扩散化学导向线索，这被认为在多细胞形态发生中很重要。在这里，我们揭示了 cAMP 介导的信号转导的动力学在细胞发育过程中从传播波转变为稳态。细胞质 cAMP 水平的活细胞成像显示，在细胞聚集和丘形成阶段，它们在细胞群体中的振荡和传播是明显的，但当多细胞蛞蝓开始迁移时，它们逐渐消失。磷酸肌醇 3,4,5-三磷酸信号转导也发生了类似的信号动力学转变，它是 cAMP 信号通路的上游。这种转变是随着发育的进行而编程的。我们提出了一个新模型，其中细胞之间的 cAMP 振荡和传播在单细胞阶段很重要，但在多细胞阶段的细胞集体迁移中是不必要的。
