PUBLICATION
Impaired caudal fin-fold regeneration in zebrafish deficient for the tumor suppressor Pten
- Authors
- Hale, A.J., Kiai, A., Sikkens, J., den Hertog, J.
- ID
- ZDB-PUB-180105-2
- Date
- 2017
- Source
- Regeneration (Oxford, England) 4: 217-226 (Journal)
- Registered Authors
- den Hertog, Jeroen
- Keywords
- PTEN, PTP, regeneration, zebrafish
- MeSH Terms
- none
- PubMed
- 29299324 Full text @ Regeneration (Oxf)
Citation
Hale, A.J., Kiai, A., Sikkens, J., den Hertog, J. (2017) Impaired caudal fin-fold regeneration in zebrafish deficient for the tumor suppressor Pten. Regeneration (Oxford, England). 4:217-226.
Abstract
Zebrafish are able to completely regrow their caudal fin-folds after amputation. Following injury, wound healing occurs, followed by the formation of a blastema, which produces cells to replace the lost tissue in the final phase of regenerative outgrowth. Here we show that, surprisingly, the phosphatase and tumor suppressor Pten, an antagonist of phosphoinositide-3-kinase (PI3K) signaling, is required for zebrafish caudal fin-fold regeneration. We found that homozygous knock-out mutant (ptena-/-ptenb-/- ) zebrafish embryos, lacking functional Pten, did not regenerate their caudal fin-folds. AKT phosphorylation was enhanced, which is consistent with the function of Pten. Reexpression of Pten, but not catalytically inactive mutant Pten-C124S, rescued regeneration, as did pharmacological inhibition of PI3K. Blastema formation, determined by in situ hybridization for the blastema marker junbb, appeared normal upon caudal fin-fold amputation of ptena-/-ptenb-/- zebrafish embryos. Whole-mount immunohistochemistry using specific markers indicated that proliferation was arrested in embryos lacking functional Pten, and that apoptosis was enhanced. Together, these results suggest a critical role for Pten by limiting PI3K signaling during the regenerative outgrowth phase of zebrafish caudal fin-fold regeneration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping