Chemical genetics of regeneration: Contrasting temporal effects of CoCl2 on axolotl tail regeneration

Nour W.Al Haj Baddar, Varun B. Dwaraka, Larissa V. Ponomareva, Jon S. Thorson, S. Randal Voss

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Background: Histone deacetylases (HDACs) regulate transcriptional responses to injury stimuli that are critical for successful tissue regeneration. Previously we showed that HDAC inhibitor romidepsin potently inhibits axolotl tail regeneration when applied for only 1-minute postamputation (MPA). Results: Here we tested CoCl2, a chemical that induces hypoxia and cellular stress, for potential to reverse romidepsin inhibition of tail regeneration. Partial rescue of regeneration was observed among embryos co-treated with romidepsin and CoCl2 for 1 MPA, however, extending the CoCl2 dosage window either inhibited regeneration (CoCl2:0 to 30 MPA) or was lethal (CoCl2:0 to 24 hours postamputation; HPA). CoCl2:0 to 30 MPA caused tissue damage, tissue loss, and cell death at the distal tail tip, while CoCl2 treatment of non-amputated embryos or CoCl2:60 to 90 MPA treatment after re-epithelialization did not inhibit tail regeneration. CoCl2-romidepsin:1 MPA treatment partially restored expression of transcription factors that are typical of appendage regeneration, while CoCl2:0 to 30 MPA significantly increased expression of genes associated with cell stress and inflammation. Additional experiments showed that CoCl2:0 to 1 MPA and CoCl2:0 to 30 MPA significantly increased levels of glutathione and reactive oxygen species, respectively. Conclusion: Our study identifies a temporal window from tail amputation to re-epithelialization, within which injury activated cells are highly sensitive to CoCl2 perturbation of redox homeostasis.

Original languageEnglish
Pages (from-to)852-865
Number of pages14
JournalDevelopmental Dynamics
Volume250
Issue number6
DOIs
StatePublished - Jun 2021

Bibliographical note

Funding Information:
Preliminary dose-response experiments were performed by undergraduate researchers enrolled in StemCats BIO-199 at University of Kentucky. This research was funded by the National Institutes of Health through their support of this project (R24OD21479), the Ambystoma Genetic Stock Center (P40OD019794), the Center of Biomedical Research Excellence (COBRE) in Pharmaceutical Research and Innovation (P20GM130456) and the National Center for Advancing Translational Sciences (UL1TR000117 and UL1TR001998).

Funding Information:
Preliminary dose‐response experiments were performed by undergraduate researchers enrolled in StemCats BIO‐199 at University of Kentucky. This research was funded by the National Institutes of Health through their support of this project (R24OD21479), the Ambystoma Genetic Stock Center (P40OD019794), the Center of Biomedical Research Excellence (COBRE) in Pharmaceutical Research and Innovation (P20GM130456) and the National Center for Advancing Translational Sciences (UL1TR000117 and UL1TR001998).

Publisher Copyright:
© 2021 American Association of Anatomists

Keywords

  • CoCl
  • axolotl
  • chemical genetics
  • hypoxia
  • tail regeneration

ASJC Scopus subject areas

  • Developmental Biology

Fingerprint

Dive into the research topics of 'Chemical genetics of regeneration: Contrasting temporal effects of CoCl2 on axolotl tail regeneration'. Together they form a unique fingerprint.

Cite this