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Significance Membrane and cytoskeletal dynamics are critical to cell motility. Extensively studied in cell culture, their roles in cell movement in vivo are less understood, especially in higher vertebrates. We use dynamic imaging to visualize membrane and cytoskeletal behavior in migrating neural crest cells in living tissue. We found that forward movement of individual neural crest cells is accompanied by circular membrane flow, from anterior-to-posterior apically and posterior-to-anterior basally, coupled with internalization of lipid vesicles via macropinocytosis in the soma. Macropinosomes become wrapped with actin, then undergo anterograde translocation via microtubules toward the lamellipodium, resulting in its expansion. We elucidate how actin dynamics and membrane flow are interacted to drive forward locomotion of individual cells.

Macropinocytosis-mediated membrane recycling drives neural crest migration by delivering F-actin to the lamellipodium