Cadherin-Mediated Cell Coupling Coordinates Chemokine Sensing across Collectively Migrating Cells
Cadherin-Mediated Cell Coupling Coordinates Chemokine Sensing across Collectively Migrating Cells
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DOI：
10.1016/j.cub.2019.06.061
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发表时间：
2019-08-05
期刊：
影响因子：
9.2
通讯作者：
Knaut, Holger
中科院分区：
文献类型：
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作者：
Colak-Champollion, Tugba;Lan, Ling;Knaut, Holger
细胞的定向迁移塑造了胚胎，有助于成人的动态平衡，当调控失调时，会导致许多疾病[1，2]。在这些过程中，细胞可以单独运动，也可以集体运动。在这两种情况下，它们都遵循引导线索，引导它们到达目的地[3-6]。与单个细胞不同，集体迁移的细胞需要与相邻细胞协调，才能一起朝着同一方向移动。最近的研究表明，前导细胞感知引导信号，将方向信息传递给后端的跟随细胞，并能沿[7-19]方向拉动跟随细胞。通过这种方式，领导细胞控制集体，并设定集体的整体速度。然而，追随者细胞是否也参与集体的转向和速度设定在很大程度上还不清楚。利用嵌合体，我们分析了领导细胞和跟随细胞在集体迁徙的斑马鱼后侧线原基中的作用。该组织表达趋化因子受体CXCR4，并由趋化因子Cxcl12a[20-23]引导。我们发现，领导细胞和跟随细胞需要感知吸引剂Cxcl12a才能有效迁移，它们通过钙粘附素相互偶联，并需要耦合才能拉动Cxcl12a不敏感的细胞。对嵌合和蛋白质缺失原基的细胞动力学分析表明，Cxcl12a传感和钙粘附素介导的黏附共同促进了单细胞和组织水平的直接迁移。这些结果表明，原基中的所有细胞都需要感知引诱剂并相互粘连，以协调它们的运动，并以强大的方向性迁移。
The directed migration of cells sculpts the embryo, contributes to homeostasis in the adult, and, when dysregulated, underlies many diseases [1, 2]. During these processes, cells move singly or as a collective. In both cases, they follow guidance cues, which direct them to their destination [3-6]. In contrast to single cells, collectively migrating cells need to coordinate with their neighbors to move together in the same direction. Recent studies suggest that leader cells in the front sense the guidance cue, relay the directional information to the follower cells in the back, and can pull the follower cells along [7-19]. In this manner, leader cells steer the collective and set the collective's overall speed. However, whether follower cells also participate in steering and speed setting of the collective is largely unclear. Using chimeras, we analyzed the role of leader and follower cells in the collectively migrating zebrafish posterior lateral line primordium. This tissue expresses the chemokine receptor Cxcr4 and is guided by the chemokine Cxcl12a [20-23]. We find that leader and follower cells need to sense the attractant Cxcl12a for efficient migration, are coupled to each other through cadherins, and require coupling to pull Cxcl12a-insensitive cells along. Analysis of cell dynamics in chimeric and protein-depleted primordia shows that Cxcl12a-sensing and cadherin-mediated adhesion contribute jointly to direct migration at both single-cell and tissue levels. These results suggest that all cells in the primordium need to sense the attractant and adhere to each other to coordinate their movements and migrate with robust directionality.