77 Oral - Cell Biology II
Friday April 08, 11:45 AM - 12:00 PM

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


Authors:
Audrey Williams; Seth Donoughe; Edwin Munro; Sally Horne-Badovinac

Affiliation: University of Chicago

Keywords:
r. cell migration; q. epithelial sheets

Many epithelial tissues form tubes and spheres, rather than the sheets often studied using epithelial cell culture models. Despite their closed topology, examples of spherical or tubular tissues undergoing collective cell migrations have emerged. The follicle cells of the ellipsoidal Drosophila egg chamber undergo one such collective migration. These epithelial cells, which make up the outermost cell layer of the egg chamber, migrate along an encapsulating basement membrane with high directional persistence for days. In the absence of a free edge or another guidance cue to dictate their migration direction, they must coordinate their migration through local interactions within the migrating cohort. One important regulator of follicle cell migration is the atypical cadherin Fat2, which localizes to the trailing edge of each cell and promotes leading edge protrusion of the cell behind. Another is the WAVE regulatory complex, which templates the formation of lamellipodial protrusions at each cell's leading edge. Using genetic manipulations, live imaging, and quantitative image analysis, we show that Fat2 polarizes protrusive activity in trans by concentrating the WAVE complex at the leading edge, across the cell-cell interface. Without this cue from Fat2, the WAVE complex remains active and the cells are protrusive, but protrusive sites fluctuate around the cell periphery and collective cell migration fails. To stabilize the orientation of WAVE complex enrichment and protrusive activity, clusters of Fat2 recruit the WAVE complex to corresponding clusters just across the cell-cell interface, at the tips of filopodia embedded within the lamellipodium. Because the Fat2-WAVE complex signaling system is deployed at each leading-trailing interface in a planar polarized manner, it both polarizes protrusions within individual cells and couples these individual cell polarities across the epithelium. This allows the cells to exert force in a common direction and achieve a highly coordinated collective cell migration.