GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE318nnn/GSE318689/primaryOK200TranscriptomicsDanio rerioExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318689GEOGSEfalseIntracellular pH dynamics promotes zebrafish larval tail regenerationIntracellular pH (pHi) dynamics regulates numerous cell behaviors, including migration and proliferation. 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. Finally, we showed that the regeneration defects in larvae with disrupted pHi were partially rescued by the GSK3 inhibitor BIO. Our data reveal a previously unrecognized role for pHi dynamics in coordinating tissue behaviors in vivo and enabling zebrafish larval tail regeneration.2026/05/14GSE318689GSM9500785GSM9500795GSM9500784GSM9500783GSM9500794GSM9500793GSM9500782GSM9500781GSM9500792GSM9500780GSM9500791GSM9500790GSM9500779GSM9500778GSM9500789GSM9500788GSM9500777GSM9500787GSM9500776GSM9500775GSM950078634622318689Danio rerio