HDAC Activity Is Required during Xenopus Tail Regeneration

PLoS ONE, 2011 · DOI: 10.1371/journal.pone.0026382 · Published: October 14, 2011

Simple Explanation

The ability to regenerate lost body parts is limited to certain animals. This study focuses on the Xenopus tadpole tail, which can fully regenerate after amputation, containing various tissues like epidermis, muscle, and spinal cord. The study investigates the role of histone deacetylases (HDACs), enzymes involved in chromatin remodeling, during tail regeneration. HDAC activity is shown to be crucial for the early stages of this process. Blocking HDAC activity with drugs like Trichostatin A (TSA) inhibits tail regeneration. This inhibition leads to changes in the expression of genes like Notch1 and BMP2, which are important for tail regeneration.

Study Duration

7 days

Participants

Xenopus laevis larvae (tadpoles)

Evidence Level

Not specified

Key Findings

1
HDAC1 is expressed during the first two days of tail regeneration in mesenchymal cells of the regeneration bud.
2
Pharmacological inhibition of HDACs using TSA or valproic acid blocks tail regeneration in Xenopus tadpoles.
3
Inhibition of HDAC function results in aberrant expression of Notch1 and BMP2, two genes required for tail regeneration.

Research Summary

This study investigates the role of histone deacetylases (HDACs) in Xenopus tadpole tail regeneration. It demonstrates that HDAC activity, particularly that of HDAC1, is required for the early stages of tail regeneration. The researchers found that blocking HDAC activity using pharmacological inhibitors like Trichostatin A (TSA) and valproic acid significantly inhibits tail regeneration. This inhibition is associated with altered histone acetylation levels and mis-expression of key regenerative genes, Notch1 and BMP2. The study also suggests that HDACs likely associate with the transcriptional repressor Mad3 to regulate histone acetylation, further highlighting the complex epigenetic regulation involved in appendage regeneration.

Practical Implications

Regenerative Medicine

Understanding the role of HDACs in appendage regeneration may provide insights for promoting tissue repair in non-regenerative tissues.

Epigenetic Therapies

Modulating histone acetylation could be a potential therapeutic strategy for enhancing regenerative processes.

Gene Regulation

HDACs are critical for proper regulation of gene expression patterns during regeneration.

Study Limitations

1
The study primarily focuses on HDAC1, and additional unidentified HDACs may also participate in regeneration.
2
The direct regulation of Notch1 and BMP2 by histone acetylation is unlikely to account for the regenerative failure due to HDAC inhibition. Other genes are likely involved.
3
Global studies of acetylation states and corresponding microarray studies are needed to fully understand the interplay between genetic, epigenetic, and bioelectrical programs.

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