Comparative gene expression profiling between optic nerve and spinal cord injury in Xenopus laevis reveals a core set of genes inherent in successful regeneration of vertebrate central nervous system axons

BMC Genomics, 2020 · DOI: https://doi.org/10.1186/s12864-020-06954-8 · Published: August 6, 2020

Regenerative Medicine Neurology Bioinformatics

Simple Explanation

This study explores why some nerve cells regenerate after injury while others don't, using the frog Xenopus laevis as a model. Frogs can regenerate optic nerve axons but lose the ability to regenerate spinal cord axons as they grow. The researchers compared gene expression in regenerating and non-regenerating nerve tissues after injury to identify genes crucial for successful regeneration. They found a core set of genes shared by regenerating tissues but not by non-regenerating ones, suggesting these genes are key to nerve regeneration.

Study Duration

3 time points: 3 days, 1 week/11 days, and 3 weeks

Participants

Xenopus laevis tadpoles and juvenile frogs (albino strain)

Evidence Level

Not specified

Key Findings

1
A set of 324 genes ("DESR genes") were differentially expressed in regenerative CNS regions (optic nerve and tadpole spinal cord) but not in non-regenerative regions.
2
The KEGG Adipocytokine signaling pathway, which links leptin with metabolic and gene regulatory pathways, was implicated as an important hub in successful CNS axon regeneration.
3
A novel gene regulatory network with genes regulating chromatin accessibility was identified as a core component in successful CNS axon regeneration.

Research Summary

This study identifies deep, phylogenetically conserved commonalities between CNS axon regeneration and other examples of successful tissue regeneration and provides new targets for studying the molecular underpinnings of successful CNS axon regeneration. The study also provides a guide for distinguishing pro-regenerative injury-induced changes in gene expression from detrimental ones in mammals. Network analyses identified the Adipocytokine signaling pathway and a novel gene regulatory network with epigenetic control of gene expression as important hubs.

Practical Implications

Identifies new therapeutic targets

The study identifies genes and pathways that can be targeted to promote CNS axon regeneration.

Distinguishes beneficial from detrimental responses

The study helps differentiate between gene expression changes that promote regeneration versus those that hinder it in mammals.

Highlights the importance of epigenetic control

The finding that chromatin accessibility is key to regeneration success could lead to new epigenetic-based therapies.

Study Limitations

1
Tissue-specific changes in gene expression dominated the injury responses, making it challenging to identify core regenerative genes.
2
The study focused only on annotated genes in Xenopus laevis, potentially missing novel genes or non-coding RNAs involved in regeneration.
3
Functional comparisons necessarily combined homeologs and paralogs under a single gene term, since most functional studies are done in other species

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