Jain Shreyansh, Cachoux Victoire M L, Narayana Gautham H N S, de Beco Simon, D'Alessandro Joseph, Cellerin Victor, Chen Tianchi, Heuzé Mélina L, Marcq Philippe, Mège René-Marc, Kabla Alexandre J, Lim Chwee Teck, Ladoux Benoit
Institut Jacques Monod, CNRS UMR 7592, Université de Paris, Paris 75013, France.
Mechanobiology Institute, National University of Singapore, Singapore 117411.
Nat Phys. 2020 Jul;16(7):802-809. doi: 10.1038/s41567-020-0875-z. Epub 2020 May 4.
The directed migration of cell collectives is essential in various physiological processes, such as epiboly, intestinal epithelial turnover, and convergent extension during morphogenesis as well as during pathological events like wound healing and cancer metastasis. Collective cell migration leads to the emergence of coordinated movements over multiple cells. Our current understanding emphasizes that these movements are mainly driven by large-scale transmission of signals through adherens junctions. In this study, we show that collective movements of epithelial cells can be triggered by polarity signals at the single cell level through the establishment of coordinated lamellipodial protrusions. We designed a minimalistic model system to generate one-dimensional epithelial trains confined in ring shaped patterns that recapitulate rotational movements observed in cellular monolayers and in genitalia or follicular cell rotation. Using our system, we demonstrated that cells follow coordinated rotational movements after the establishment of directed Rac1-dependent polarity over the entire monolayer. Our experimental and numerical approaches show that the maintenance of coordinated migration requires the acquisition of a front-back polarity within each single cell but does not require the maintenance of cell-cell junctions. Taken together, these unexpected findings demonstrate that collective cell dynamics in closed environments as observed in multiple and situations can arise from single cell behavior through a sustained memory of cell polarity.
细胞集体迁移在多种生理过程中至关重要,如在形态发生过程中的外包、肠上皮更新以及汇聚延伸,以及在诸如伤口愈合和癌症转移等病理事件中。集体细胞迁移导致多个细胞出现协调运动。我们目前的理解强调,这些运动主要由通过黏附连接的大规模信号传递驱动。在本研究中,我们表明上皮细胞的集体运动可通过在单细胞水平上建立协调的片状伪足突起,由极性信号触发。我们设计了一个简约的模型系统,以生成一维上皮细胞列,其被限制在环形模式中,重现了在细胞单层以及生殖器或卵泡细胞旋转中观察到的旋转运动。使用我们的系统,我们证明在整个单层建立定向的Rac1依赖性极性后,细胞会遵循协调的旋转运动。我们的实验和数值方法表明,协调迁移的维持需要在每个单细胞内获得前后极性,但不需要维持细胞间连接。综上所述,这些意外发现表明,在多种情况中观察到的封闭环境中的集体细胞动态可通过细胞极性的持续记忆,由单细胞行为产生。