Department of Biology, Yamaguchi University, Yamaguchi 753-8512, Japan.
Department of Mathematical Engineering, Musashino University, Tokyo 135-8181, Japan.
Proc Natl Acad Sci U S A. 2022 May 3;119(18):e2119903119. doi: 10.1073/pnas.2119903119. Epub 2022 Apr 27.
Collective cell migration is seen in many developmental and pathological processes, such as morphogenesis, wound closure, and cancer metastasis. When a fish scale is detached and adhered to a substrate, epithelial keratocyte sheets crawl out from it, building a semicircular pattern. All the keratocytes at the leading edge of the sheet have a single lamellipodium, and are interconnected with each other via actomyosin cables. The leading edge of the sheet becomes gradually longer as it crawls out from the scale, regardless of the cell-to-cell connections. In this study, we found leading-edge elongation to be realized by the interruption of follower cells into the leading edge. The follower cell and the two adjacent leader cells are first connected by newly emerging actomyosin cables. Then, the contractile forces along the cables bring the follower cell forward to make it a leader cell. Finally, the original cables between the two leader cells are stretched to tear by the interruption and the lamellipodium extension from the new leader cell. This unique actomyosin-cable reconnection between a follower cell and adjacent leaders offers insights into the mechanisms of collective cell migration.
细胞集体迁移可见于许多发育和病理过程中，例如形态发生、伤口愈合和癌症转移。当鱼鳞片脱落并附着在基质上时，上皮角质细胞片从鳞片中爬出，形成半圆形图案。片层前缘的所有角质细胞都有一个单一的片状伪足，并且通过肌动球蛋白电缆相互连接。当片层从鳞片中爬出时，片层的前缘会逐渐变长，而不管细胞间的连接如何。在这项研究中，我们发现前缘的伸长是通过跟随细胞中断进入前缘来实现的。首先，新出现的肌动球蛋白电缆将跟随细胞与两个相邻的先导细胞连接起来。然后，沿着电缆的收缩力将跟随细胞向前移动，使其成为先导细胞。最后，原始电缆在中断和新先导细胞的片状伪足延伸的作用下被拉伸撕裂。这种跟随细胞与相邻先导细胞之间独特的肌动球蛋白电缆重新连接为细胞集体迁移的机制提供了新的见解。
