Integration of Migratory Cells into a New Site In Vivo Requires Channel-Independent Functions of Innexins on Microtubules

Integration of Migratory Cells into a New Site In Vivo Requires Channel-Independent Functions of Innexins on Microtubules
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DOI:
10.1016/j.devcel.2020.06.024
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发表时间:
2020-08-24
期刊:
影响因子:
11.8
通讯作者:
Montell, Denise J.
Montell, Denise J.
中科院分区:
生物学1区
文献类型:
--
作者:
Miao, Guangxia;Godt, Dorothea;Montell, Denise J.

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在胚胎发育和癌症转移过程中,迁移细胞必须与目的地的新伴侣建立稳定的连接。在这里,我们建立了果蝇边界细胞作为这个多步骤过程的模型。在卵子发生过程中,边缘细胞从卵泡上皮中脱层并迁移。当它们到达它们的目标卵母细胞时,它们经历一系列常规步骤粘附在卵母细胞上,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的关键。令人惊讶的是,通道功能是可扩展的。相反,Innexin 2和3在边缘细胞内起作用,Innexin 4在生殖细胞内起作用,以调节微管。微管依赖的边缘细胞的相互作用是必不可少的支撑细胞对外部形态发生的力量。因此,我们建立了一个实验模型,并使用遗传学,热遗传学和活体成像方法来揭示Innexins和微管对发育和癌症中重要的细胞生物学过程的贡献。
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 celloocyte 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.