Intracellular pH dynamics promotes zebrafish larval tail regeneration

While these functions are well-established in cell lines, the role of pHi changes in vivo is less well understood. We generated a transgenic zebrafish line expressing a fluorescent ratiometric pHi biosensor and identified functional changes in pHi during zebrafish larval tail regeneration.

We found that tail amputation led to a transient decrease in pHi, followed by a prolonged increase in pHi above pre-amputation values. Moreover, we showed that pharmacologically inhibiting Na+/H+ exchanger (NHE) activity or decreasing extracellular pH attenuated the post-amputation increase in pHi, reduced subsequent cell proliferation, and impaired tail regeneration. We further found that inhibiting NHE activity post-amputation led to elevated inflammation, disrupted myeloid cell behavior, decreased reactive oxygen species, and increased glycogen synthase kinase-3 (GSK3) activity.