Molecular, Cellular, and Developmental Biology Department, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Department of Cell and Systems Biology, University of Toronto, 25 Harbord Street, Toronto, ON M5S 3G5, Canada.
Dev Cell. 2020 Aug 24;54(4):501-515.e9. doi: 10.1016/j.devcel.2020.06.024. Epub 2020 Jul 14.
During embryonic development and cancer metastasis, migratory cells must establish stable connections with new partners at their destinations. Here, we establish the Drosophila border cells as a model for this multistep process. During oogenesis, border cells delaminate from the follicular epithelium and migrate. When they reach their target, the oocyte, they undergo a stereotypical series of steps to adhere to it, then connect with another migrating epithelium. We identify gap-junction-forming innexin proteins as critical. Surprisingly, the channel function is dispensable. Instead, Innexins 2 and 3 function within the border cells, and Innexin 4 functions within the germline, to regulate microtubules. The microtubule-dependent border cell-oocyte interaction is essential to brace the cells against external morphogenetic forces. Thus, we establish an experimental model and use genetic, thermogenetic, and live-imaging approaches to uncover the contributions of Innexins and microtubules to a cell-biological process important in development and cancer.
在胚胎发育和癌症转移过程中，迁移细胞必须在目的地与新的伙伴建立稳定的连接。在这里，我们将果蝇的边缘细胞确立为这一多步过程的模型。在卵子发生过程中，边缘细胞从滤泡上皮层分离并迁移。当它们到达目标卵母细胞时，它们会经历一系列典型的步骤与之粘附，然后与另一个迁移的上皮细胞连接。我们确定间隙连接形成的连接蛋白作为关键。令人惊讶的是，通道功能是可有可无的。相反，连接蛋白 2 和 3 在边缘细胞内发挥作用，而连接蛋白 4 在生殖系内发挥作用，以调节微管。微管依赖性的边缘细胞-卵母细胞相互作用对于支撑细胞抵御外部形态发生力至关重要。因此，我们建立了一个实验模型，并使用遗传、热遗传和活体成像方法来揭示连接蛋白和微管对发育和癌症中重要的细胞生物学过程的贡献。
