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Lamellipodia-like protrusions and focal adhesions contribute to collective cell migration in zebrafish
Developmental Biology ( IF 2.5 ) Pub Date : 2020-10-21 , DOI: 10.1016/j.ydbio.2020.10.007
Hannah M Olson 1 , Alex V Nechiporuk 2
Affiliation  

Collective cell migration is a process where cohorts of cells exhibit coordinated migratory behavior. During individual and collective cellular migration, cells must extend protrusions to interact with the extracellular environment, sense chemotactic cues, and act as points of attachment. The mechanisms and regulators of protrusive behavior have been widely studied in individually migrating cells; however, how this behavior is regulated throughout collectives is not well understood. To address this, we used the zebrafish posterior lateral line primordium (pLLP) as a model. The pLLP is a cluster of ∼150 cells that migrates along the zebrafish trunk, depositing groups of cells that will become sensory organs. To define protrusive behavior, we performed mosaic analysis to sparsely label pLLP cells with a transgene marking filamentous actin. This approach revealed an abundance of brush-like protrusions throughout the pLLP that orient in the direction of migration. Formation of these protrusions depends on the Arp2/3 complex, a regulator of dendritic actin. This argues that these brush-like protrusions are an in vivo example of lamellipodia. Mosaic analysis demonstrated that these lamellipodia-like protrusions are located in a close proximity to the overlying skin. Immunostaining revealed an abundance of focal adhesion complexes surrounding the pLLP. Disruption of these complexes specifically in pLLP cells led to impaired pLLP migration. Finally, we show that Erk signaling, a known regulator of focal adhesions, is required for proper formation of lamellipodia-like protrusions in pLLP cells and pLLP migration. Altogether, our results suggest a model where the coordinated dynamics of lamellipodia-like protrusions, making contact with either the overlying skin or the extracellular matrix through focal adhesions, promotes migration of pLLP cells.



中文翻译:

片状伪足样突起和粘着斑有助于斑马鱼的集体细胞迁移

集体细胞迁移是细胞群表现出协调的迁移行为的过程。在个体和集体细胞迁移过程中,细胞必须延伸突起以与细胞外环境相互作用,感知趋化线索,并充当附着点。突出行为的机制和调节因子已在个体迁移细胞中得到广泛研究;然而,这种行为如何在整个集体中受到监管尚不清楚。为了解决这个问题,我们使用斑马鱼后侧线原基 (pLLP) 作为模型。pLLP 是一簇约 150 个细胞,沿着斑马鱼躯干迁移,沉积成群的细胞,这些细胞将成为感觉器官。为了定义突出行为,我们进行了镶嵌分析,用转基因标记丝状肌动蛋白稀疏地标记 pLLP 细胞。这种方法揭示了整个 pLLP 中大量的刷状突起,这些突起朝向迁移方向。这些突起的形成取决于树突状肌动蛋白的调节剂 Arp2/3 复合物。这认为这些刷状突起是片状伪足的体内例子。马赛克分析表明,这些片状伪足状突起位于紧邻上覆皮肤的位置。免疫染色显示 pLLP 周围有大量粘着斑复合物。这些复合物在 pLLP 细胞中的破坏会导致 pLLP 迁移受损。最后,我们表明 Erk 信号传导是一种已知的粘着斑调节剂,它是 pLLP 细胞中板状伪足样突起的正确形成和 pLLP 迁移所必需的。总而言之,我们的研究结果提出了一个模型,其中板状伪足样突起的协调动力学通过粘着斑与上覆皮肤或细胞外基质接触,促进 pLLP 细胞的迁移。

更新日期:2020-10-30
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