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

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.

Keywords: Drosophila; border cells; cell migration; channel-independent; gap junction; innexin; microtubule; morphogenesis; neolamination; oogenesis.