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Published on: January 31, 2015
Intracellular pH dynamics promotes zebrafish larval tail regeneration.
Cambria Chou-Freed1, Christopher K Prinz2, Anush Margaryan3
1Department of Cell and Tissue Biology, University of California San Francisco, San Francisco, CA, 94143, USA.
Developmental Biology
|July 8, 2026
Summary
Zebrafish tail regeneration involves dynamic intracellular pH (pHi) changes. Inhibiting the Na+/H+ exchanger (NHE) disrupts this pHi regulation, leading to impaired regeneration and increased inflammation.
Area of Science:
- Regenerative Biology
- Cellular Physiology
- Zebrafish Models
Background:
- Intracellular pH (pHi) regulates critical cellular functions like migration and proliferation.
- The role of pHi dynamics in vivo, particularly during regeneration, remains less understood compared to cell line studies.
Purpose of the Study:
- To investigate the role of intracellular pH (pHi) dynamics during zebrafish larval tail regeneration.
- To identify the molecular mechanisms linking pHi changes to regenerative processes.
Main Methods:
- Generated a transgenic zebrafish line expressing a fluorescent ratiometric pHi biosensor.
- Utilized pharmacological inhibitors (Na+/H+ exchanger inhibitors) and extracellular pH manipulation.
- Assessed cell proliferation, inflammation, myeloid cell behavior, reactive oxygen species, and GSK3 activity.
Main Results:
- Tail amputation induced transient pHi decrease followed by a sustained increase.
- Inhibiting Na+/H+ exchanger (NHE) activity or lowering extracellular pH impaired regeneration by reducing cell proliferation.
- NHE inhibition increased inflammation, altered myeloid cell behavior, decreased reactive oxygen species, and elevated GSK3 activity.
- GSK3 inhibitors partially rescued regeneration defects in larvae with disrupted pHi.
Conclusions:
- pHi dynamics play a crucial, previously unrecognized role in coordinating tissue behaviors during in vivo regeneration.
- Na+/H+ exchanger activity is essential for maintaining pHi homeostasis and enabling zebrafish tail regeneration.
- GSK3 signaling is implicated in the pHi-mediated regulation of zebrafish tail regeneration.
