V-ATPase proton pumping in regeneration

D'Arcy Thompson's work on tail regeneration concerns rate, not proton pumps. In On Growth and Form, he built a diagram of the linear rate of regeneration from data given by Ellis on tadpoles¹. Ellis's tadpoles were of similar size, with tails near 26 mm, or 65 per cent of body length. In four series about 10, 20, 40 and 60 per cent of the tail was removed, and the amount regrown was tabulated in three-day intervals¹. Thompson plotted these amounts against time to interpolate how long definite percentages took to regenerate¹.

Monteiro and colleagues (2014) built on their own earlier suggestion that V-ATPase mediates the regeneration-specific H+ efflux, and tested it in this paper. They reasoned that V-ATPase expression along the PD axis should be matched by an H+ efflux pattern². Measuring H+ flux after amputation with SIET, they found that efflux always peaked at 24 hours post amputation. In proximal stumps it began earlier, at 3 hours rather than 12, and was significantly higher than in distal regions³. They took this to extend the correlation to position-dependent regeneration rate³. Expression and efflux both seemed stronger during blastema formation and fell afterwards, which they said suggests a causal relation⁴.

Tyler's 2017 review collects this work. It reports that driving H+ efflux in non-regenerating Xenopus tadpole tails can trigger regeneration, citing Masuda and Montero-Lomeli (2000). Tyler reads this as suggesting that the bioelectric signal activates a positional information pathway or carries instructional information⁵. The review also cites the zebrafish caudal fin work as showing V-ATPase involvement in position-dependent cues⁵. It adds a caution. Highly regenerative animals may rely on divergent mechanisms that may not translate to mammals. Tyler still proposes that differences in bioelectric signalling may partly explain failed regeneration in humans⁶.

Outside regeneration, V-ATPase distribution has been tied to bioelectric patterns. Krüger and Bohrmann (2015) found V-ATPases accumulated on the ventral side of Drosophila follicles at stages S9 to S10B. They noted that this matches the dorsoventral Vmem pattern and suggested a role in setting spatial coordinates⁷. Funk (2015) cites Vandenberg et al. (2012), who saw voltage gradients in Xenopus craniofacial patterning driven by regionally different V-ATPase activity⁸. Pai and colleagues (2025) found V-ATPase upregulated in Xenobots, in a metabolism cluster, and noted its known regulation of mitochondrial metabolism⁹.