Chemical Genetics of Regeneration: Contrasting Temporal Effects of CoCl2 on Axolotl Tail Regeneration

Dev Dyn, 2021 · DOI: 10.1002/dvdy.294 · Published: June 1, 2021

Pharmacology Regenerative Medicine Genetics

Simple Explanation

This study investigates how a chemical, CoCl2, impacts tail regeneration in axolotls, particularly when combined with another chemical, romidepsin, which inhibits regeneration. They found that timing of CoCl2 exposure is critical: brief exposure can partially reverse romidepsin's effects, but prolonged exposure inhibits regeneration or is lethal. The researchers observed that CoCl2's negative effects on regeneration were only present when applied shortly after tail amputation, before the wound had closed. This suggests a specific window of vulnerability during the early stages of regeneration. Gene expression analysis revealed that CoCl2 alters the expression of genes related to stress, inflammation, and oxygen levels, especially when applied during this sensitive window. This indicates that CoCl2 disrupts the normal cellular processes needed for successful regeneration.

Study Duration

Not specified

Participants

Developmental stage 42 axolotl embryos

Evidence Level

Not specified

Key Findings

1
CoCl2 can partially rescue the inhibitory effect of romidepsin on tail regeneration when co-administered for 1 minute post-amputation (MPA).
2
Prolonged CoCl2 treatment (0-30 MPA) inhibits tail regeneration and causes tissue damage, tissue loss, and cell death at the distal tail tip.
3
CoCl2 treatment significantly increases levels of glutathione and reactive oxygen species, depending on the duration of exposure.

Research Summary

This study investigates the effects of CoCl2, a chemical that induces hypoxia and cellular stress, on axolotl tail regeneration, particularly in the context of romidepsin-induced regeneration inhibition. The researchers found that the timing of CoCl2 administration is critical, with brief co-treatment partially rescuing regeneration inhibited by romidepsin, while prolonged exposure inhibits regeneration or is lethal. Gene expression analysis reveals that CoCl2 affects the expression of genes related to stress, inflammation, and oxygen levels, especially when applied during the early stages of wound healing and re-epithelialization.

Practical Implications

Temporal Sensitivity

The study highlights the importance of considering the timing of chemical exposures when studying regeneration, as different time windows may have opposing effects.

Redox Homeostasis

The findings suggest that maintaining proper redox balance is crucial for successful regeneration, and disruption of this balance by CoCl2 can impair the process.

Drug Interactions

The study demonstrates that chemical interactions can have complex effects on regeneration, with one chemical (CoCl2) able to partially rescue the effects of another (romidepsin) under specific conditions.

Study Limitations

1
The study focuses on a single chemical (CoCl2) and its interaction with romidepsin, limiting the generalizability of the findings.
2
The molecular mechanisms underlying the observed effects of CoCl2 are not fully elucidated, requiring further investigation.
3
The study is conducted in axolotl embryos, and the results may not be directly applicable to adult axolotls or other regenerative models.

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