Collective migration of epithelial cells underlies diverse tissue-remodeling events, but the mechanisms that coordinate individual cell migratory behaviors for collective movement are largely unknown. Studying the Drosophila follicular epithelium, we show that the cadherin Fat2 and the receptor tyrosine phosphatase Lar function in a planar signaling system that coordinates leading and trailing edge dynamics between neighboring cells. Fat2 signals from each cell's trailing edge to induce leading edge protrusions in the cell behind, in part by stabilizing Lar's localization in these cells. Conversely, Lar signals from each cell's leading edge to stimulate trailing edge retraction in the cell ahead. Fat2/Lar signaling is similar to planar cell polarity signaling in terms of sub-cellular protein localization; however, Fat2/Lar signaling mediates short-range communication between neighboring cells instead of transmitting long-range information across a tissue. This work defines a key mechanism promoting epithelial migration and establishes a different paradigm for planar cell-cell signaling.
Bibliographical noteFunding Information:
We thank the flyCRISPR group at UW-Madison for advice, Yi Guo, Jennifer Zallen, and Allan Spradling for Drosophila stocks, Ben Glick for 3xGFP plasmid, Darcy Andersen and Kayla Muirhead for experimental assistance, and Nick Badovinac and Nate Ellis for illustrations. We thank Benoit Aiguoy for providing Packing Analyzer, and Wen Yih Aw, Bryan Heck, and Danelle Devenport for providing the MATLAB script to normalize and plot polarity data. Ellie Heckscher, Chip Ferguson, Ed Munro, Volodya Gelfand, and members of the Horne-Badovinac lab provided valuable comments on the manuscript. K.B. is an HHMI Fellow of the Life Sciences Research Foundation. This work was further supported by NIH grants T32 GM007183 (to M.C.) and R01 GM094276 (to S.H.-B.).
© 2017 Elsevier Inc.
- collective cell migration
- egg chamber