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Fat2 polarizes the WAVE complex in trans to align cell protrusions for collective migration

View ORCID ProfileAudrey M. Williams, View ORCID ProfileSeth Donoughe, View ORCID ProfileEdwin Munro, View ORCID ProfileSally Horne-Badovinac
doi: https://doi.org/10.1101/2022.01.17.476701
Audrey M. Williams
1Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL, USA
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Seth Donoughe
1Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL, USA
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Edwin Munro
1Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL, USA
2Committee on Development, Regeneration, and Stem Cell Biology, University of Chicago, Chicago, IL, USA
3Institute for Biophysical Dynamics, University of Chicago, Chicago, IL, USA
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Sally Horne-Badovinac
1Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL, USA
2Committee on Development, Regeneration, and Stem Cell Biology, University of Chicago, Chicago, IL, USA
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  • For correspondence: shorne@uchicago.edu
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Abstract

For a group of cells to migrate together, each cell must couple the polarity of its own migratory machinery with that of the other cells in the migrating group. Although collective cell migrations are common in animal development, it is not understood how protrusions are coherently polarized within groups of migrating epithelial cells. We address this problem in the collective migration of the Drosophila melanogaster follicular epithelial cells, demonstrating that the atypical cadherin Fat2 relays polarity information between neighboring cells, causing them to align their lamellipodia and migrate together. Fat2 localizes the WAVE complex to the leading edge of each cell, where the WAVE complex builds polarized lamellipodia. In Fat2’s absence, the WAVE complex becomes enriched at fluctuating positions around the cell perimeter, resulting in short-lived and spatially disordered protrusive regions, ultimately causing collective migration to fail. In wild-type tissue, Fat2 puncta along the trailing edge of each cell concentrate the WAVE complex in corresponding puncta just across the cell-cell interface, restricting WAVE complex activity and protrusions to one stable leading edge. In summary, migrating cells couple their protrusive activity to that of their neighbors using a polarized transmembrane cue. We propose that this mechanism enables the tissue to achieve persistent, days-long directed migration.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted January 20, 2022.
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Fat2 polarizes the WAVE complex in trans to align cell protrusions for collective migration
Audrey M. Williams, Seth Donoughe, Edwin Munro, Sally Horne-Badovinac
bioRxiv 2022.01.17.476701; doi: https://doi.org/10.1101/2022.01.17.476701
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Fat2 polarizes the WAVE complex in trans to align cell protrusions for collective migration
Audrey M. Williams, Seth Donoughe, Edwin Munro, Sally Horne-Badovinac
bioRxiv 2022.01.17.476701; doi: https://doi.org/10.1101/2022.01.17.476701

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