Using Ambystoma mexicanum (Mexican Axolotl) Embryos, Chemical Genetics, and Microarray Analysis to Identify Signaling Pathways Associated with Tissue Regeneration

Comp Biochem Physiol C Toxicol Pharmacol, 2015 · DOI: 10.1016/j.cbpc.2015.06.004 · Published: December 1, 2015

Pharmacology Regenerative Medicine Genetics

Simple Explanation

This study introduces a new model for studying tissue regeneration using Mexican axolotl embryos, which can fully regenerate amputated tails in 7 days. The researchers used a chemical screening approach to identify substances that affect tail regeneration, focusing on inhibitors of major signaling pathways. Microarray analysis was used to explore how inhibiting Wnt signaling affects multiple signaling pathways associated with tail regeneration, showing a hierarchically structured and temporally ordered transcriptional program.

Study Duration

7 days

Participants

Mexican axolotl embryos (stage 42)

Evidence Level

Not specified

Key Findings

1
Axolotl embryos can completely regenerate amputated tails in 7 days without feeding, making them an efficient model for regeneration studies.
2
Inhibition of Wnt, Tgf-β, and Fgf signaling pathways completely blocked tail regeneration in axolotl embryos.
3
Inhibition of Wnt signaling broadly affects the transcription of genes associated with multiple developmental pathways, suggesting a hierarchically structured transcriptional program.

Research Summary

The study introduces a new tail regeneration model using late-stage Mexican axolotl embryos, which can regenerate amputated tails in 7 days. Chemical screening identified Wnt, transforming growth factor beta (Tgf-β), and fibroblast growth factor (Fgf) pathway antagonists that block tail regeneration. Microarray analysis revealed that Wnt signaling inhibition affects transcription of genes across multiple developmental pathways, indicating a structured and temporally ordered regeneration program.

Practical Implications

Chemical Screening Model

The axolotl embryo model can be used for efficient chemical screening to identify molecules affecting tissue regeneration.

Signaling Pathway Insights

The study provides insights into the signaling pathways involved in tissue regeneration, particularly the role of Wnt signaling.

Comparative Regeneration Studies

The model allows for comparative studies with other regenerative models like zebrafish and Xenopus to identify conserved mechanisms.

Study Limitations

1
The study used a single dose for almost all chemicals, limiting the understanding of dose-dependent effects.
2
The study notes that the histological equivalence of the embryo model to larval tail regeneration needs further investigation.
3
The tissue sampling strategy for microarray analysis resulted in quantitative and qualitative differences between control and C59-treated embryos, which may affect interpretation.

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