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Whole Body Regeneration01:33

Whole Body Regeneration

Regeneration is the process of restoring injured or lost tissues, organs, or body parts. While simpler organisms generally show greater ability to regenerate their whole body, few complex animals show similarly exceptional regeneration. For example, planarian flatworms have a unique regenerative potential making them a popular study organism among biologists to understand the mechanisms of whole body regeneration. Other organisms, such as hydra, also show extreme regeneration potential; even...

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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
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Summary
This summary is machine-generated.

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.

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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.