Fat2 polarizes the WAVE complex in trans to align cell protrusions for collective migration
For a group of cells to migrate together, each cell must couple the polarity of its migratory machinery with that of the other cells in the cohort. Although collective cell migrations are common in animal development, little is known about how protrusions are coherently polarized among groups of migrating epithelial cells. We address this problem in the collective migration of the follicular epithelial cells in Drosophila melanogaster. In this epithelium, the cadherin Fat2 localizes to the trailing edge of each cell and promotes the formation of F-actin-rich protrusions at the leading edge of the cell behind. We show that Fat2 performs this function by acting in trans to concentrate the activity of the WASP family verprolin homolog regulatory complex (WAVE complex) at one long-lived region along each cell's leading edge. Without Fat2, the WAVE complex distribution expands around the cell perimeter and fluctuates over time, and protrusive activity is reduced and unpolarized. We further show that Fat2's influence is very local, with sub-micron-scale puncta of Fat2 enriching the WAVE complex in corresponding puncta just across the leading-trailing cell-cell interface. These findings demonstrate that a trans interaction between Fat2 and the WAVE complex creates stable regions of protrusive activity in each cell and aligns the cells' protrusions across the epithelium for directionally persistent collective migration.
The code necessary to reproduce core aspects of data analysis, along with numerical data not included in source data files, are available at https://github.com/a9w/Fat2_polarizes_WAVE (Williams and Donoughe, 2022). Sequences of plasmids generated in this study are also available at https://github.com/a9w/Fat2_polarizes_WAVE. We will share the flies or plasmids themselves upon request to the corresponding author. Image and movie data are available from https://doi.org/10.6084/m9.figshare.20759314.v1.
Fat2 polarizes the WAVE complex for collective cell migrationhttps://doi.org/10.6084/m9.figshare.20759314.v1.
Article and author information
National Institutes of Health (R01 GM126047)
- Audrey Miller Williams
National Institutes of Health (R01 HD88831)
- Edwin Munro
National Institutes of Health (T32 HD055164)
- Audrey Miller Williams
Chicago Fellows Postdoctoral Award
- Seth Donoughe
Jane Coffin Childs Postdoctoral Fellowship
- Seth Donoughe
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Derek Applewhite, Reed College, United States
- Preprint posted: January 20, 2022 (view preprint)
- Received: March 3, 2022
- Accepted: September 11, 2022
- Accepted Manuscript published: September 26, 2022 (version 1)
- Version of Record published: October 17, 2022 (version 2)
© 2022, Williams et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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