PUBLICATION
Intracellular pH Dynamics Promotes Zebrafish Larval Tail Regeneration
- Authors
- Chou-Freed, C., Prinz, C.K., Margaryan, A., Theriot, J.A., Wagner, D.E., Barber, D.L.
- ID
- ZDB-PUB-260709-5
- Date
- 2026
- Source
- Developmental Biology : S0012-1606(26)00150-8 (Journal)
- Registered Authors
- Wagner, Daniel
- Keywords
- none
- Datasets
- GEO:GSE318689
- MeSH Terms
- none
- PubMed
- 42419445 Full text @ Dev. Biol.
Citation
Chou-Freed, C., Prinz, C.K., Margaryan, A., Theriot, J.A., Wagner, D.E., Barber, D.L. (2026) Intracellular pH Dynamics Promotes Zebrafish Larval Tail Regeneration. Developmental Biology. :S0012-1606(26)00150-8.
Abstract
Intracellular pH (pHi) dynamics regulates numerous cellular processes, 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 pharmacological GSK3 inhibitors. Collectively, our data reveal a previously unrecognized role for pHi dynamics in coordinating tissue behaviors in vivo and enabling zebrafish larval tail regeneration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping