Transcriptional Correlates of Proximal-Distal Identity and Regeneration Timing in Axolotl Limbs

Comp Biochem Physiol C Toxicol Pharmacol, 2018 · DOI: 10.1016/j.cbpc.2017.10.010 · Published: June 1, 2018

Regenerative Medicine Genetics Bioinformatics

Simple Explanation

Salamander limbs can regenerate, replacing amputated tissues at different positions along the limb. The study investigates if positional memory is linked to changes in gene activity along the limb's length. The study found that after amputation, genes usually active in differentiated muscle cells decreased more rapidly in upper arms, while genes related to cell division were more active. This suggests that upper arms remodel tissue more vigorously and have a greater cell division response after amputation. The study also identified genes that might be involved in positional memory, including genes that produce epithelial proteins and molecules involved in cell surface interactions, cell adhesion, and the extracellular matrix.

Study Duration

28 days

Participants

Axolotls, 6 cm in total length

Evidence Level

Not specified

Key Findings

1
Upper arms undergo more robust tissue remodeling and cell proliferation responses after amputation, potentially explaining the similar regeneration times between proximal and distal amputations.
2
Candidate positional memory genes were identified, including those encoding epithelial proteins and molecules related to cell surface, cell adhesion, and extracellular matrix.
3
Dynamic transcriptional regulation was implicated in limb regeneration through the discovery of genes exhibiting different, bivariate patterns of gene expression between fore and upper arms.

Research Summary

This study investigates the molecular basis of positional memory and regeneration timing in axolotl limbs by examining gene expression differences between fore and upper arms during regeneration. The research identified genes expressed differently at the time of amputation and during regeneration, suggesting that upper arms undergo more robust tissue remodeling and cell proliferation responses after amputation. The study also found candidate positional memory genes and revealed dynamic transcriptional patterns, contributing to a better understanding of limb regeneration.

Practical Implications

Understanding Positional Information

Identifying genes involved in positional memory can help elucidate how cells know what structures to regenerate.

Improving Regenerative Therapies

Understanding the mechanisms that regulate regeneration timing could lead to strategies to accelerate or improve tissue repair in humans.

Epithelial Signaling in Regeneration

The discovery of differently expressed epithelial proteins suggests that the wound epidermis plays a crucial role in signaling to underlying mesenchymal cells during regeneration.

Study Limitations

1
The study focused on a limited time frame (the first 28 days of regeneration).
2
The study relied on microarray analysis, which may not capture all gene expression changes.
3
The functional roles of the identified genes need to be further investigated to confirm their involvement in positional memory and regeneration timing.

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