Stretch-induced endogenous electric fields drive directed collective cell migration in vivo

Directed collective cell migration is essential for morphogenesis, and chemical, electrical, mechanical and topological features have been shown to guide cell migration in vitro. Here we provide in vivo evidence showing that endogenous electric fields drive the directed collective cell migration of an embryonic stem cell population-the cephalic neural crest of Xenopus laevis. We demonstrate that the voltage-sensitive phosphatase 1 is a key component of the molecular mechanism, enabling neural crest cells to specifically transduce electric fields into a directional cue in vivo. Finally, we propose that endogenous electric fields are mechanically established by the convergent extension movements of the ectoderm, which generate a membrane tension gradient that opens stretch-activated ion channels. Overall, these findings establish a role for electrotaxis in tissue morphogenesis, highlighting the functions of endogenous bioelectrical stimuli in non-neural contexts.