Abstract
Cell migration is crucial for diverse biological processes. Here we have visualized the dynamics of PI(3)K activity during neutrophil migration in intact tissues, revealing that PI(3)K activation at the leading edge is critical for neutrophil motility. Rac was activated locally in living zebrafish using genetically encoded photoactivatable Rac, demonstrating that Rac activation is sufficient to direct cell migration in vivo. In PI(3)K-inhibited cells, Rac activation at the leading edge rescued membrane protrusion but not cell migration or polarity in PI(3)K-inhibited cells. Uncoupling Rac-mediated protrusion and polarization suggests a new paradigm of two-tiered PI(3)K-mediated regulation of cell motility. This work exemplifies a broadly applicable new approach for examining spatio-temporal regulation of signaling within multicellular organisms.
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