In certain contexts, voltage gradients and ion flows are known to regulate developmental patterning, but their precise role has remained ambiguous. Now, Michael Levin and colleagues report on the role of the V-ATPase H+ pump in Xenopus tail regeneration. Cells in an uncut tail have normal membrane potential levels. However, following the amputation of the tail, the regeneration bud becomes depolarised (p. 1323). Shortly after, V-ATPase expression is triggered, leading to H+ flux and to the rapid repolarisation of these cells. The genetic or biochemically induced loss of V-ATPase activity prevents tail regeneration, but not as a consequence of apoptosis. Axon patterning and tail outgrowth are restored if H+ flux is induced. This fascinating study shows that ion flows do not simply perform housekeeping duties and that, during Xenopus tail regeneration, H+ flux controls both cell number (through membrane voltage) and correct axon guidance (nerves are a known growth-factor source) into the regenerative bud. Ion pumps provide a tantalising target for future biomedical research into regeneration.
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