Highly conserved molecular pathways, including Wnt signaling, promote functional recovery from spinal cord injury in lampreys

Scientific Reports, 2018 · DOI: 10.1038/s41598-017-18757-1 · Published: January 17, 2018

Regenerative Medicine Neurology Genetics

Simple Explanation

Unlike mammals, lampreys are vertebrates that undergo spontaneous regeneration and achieve functional recovery after SCI. Therefore our goal was to determine the complete transcriptional responses that occur after SCI in lampreys and to identify deeply conserved pathways that promote regeneration. We describe complex transcriptional responses in the injured spinal cord, and somewhat surprisingly, also in the brain. Transcriptional responses to SCI in lampreys included transcription factor networks that promote peripheral nerve regeneration in mammals such as Atf3 and Jun. Pharmacological inhibition of Wnt signaling inhibited functional recovery, confirming a critical role for this pathway. These data indicate that molecular signals present in mammals are also involved in regeneration in lampreys, supporting translational relevance of the model.

Study Duration

12 Weeks

Participants

25-66 lampreys per time point

Evidence Level

Not specified

Key Findings

1
SCI in lamprey induces expression of many transcripts associated with regeneration in the mammalian PNS, illustrating the power of this organism as a model for identifying and studying highly conserved, fundamental, pro-regenerative molecular pathways.
2
SCI induces rapid, robust, and long-lasting changes in gene expression in the brain, implicating supraspinal responses as a major component of anatomical and functional recovery.
3
Wnt signaling is necessary for functional recovery in the lamprey after SCI, justifying future studies aimed at elucidating the required aspects of the Wnt pathway.

Research Summary

Results from this study reveal several key findings. First, these data reinforce lessons from the recent publication of the lamprey genome, which is that the lamprey CNS expresses homologs of a large number of mammalian CNS genes, indicating a high degree of molecular conservation across vertebrates. One of the most surprising findings from this study is the robust and complex transcriptional responses occurring in the lamprey brain after SCI. Previous studies in lamprey revealed SCI-induced changes in expression levels of genes related to axon growth and guidance within the RS neuron somata located in the brain Multiple independent bioinformatics analyses revealed that RAGs, many of which are members of the canonical and non-canonical Wnt signaling pathways, are differentially expressed after SCI in lamprey.

Practical Implications

Drug Development

Understanding the role of Wnt signaling in lamprey spinal cord regeneration could lead to new drug targets for promoting regeneration in humans.

Comparative Biology

The study highlights the value of using simpler organisms like lampreys to understand fundamental biological processes like regeneration.

Therapeutic Strategies

Identifying conserved molecular pathways could help develop more effective therapeutic strategies for spinal cord injury in mammals.

Study Limitations

1
The current lamprey reference transcriptome is incomplete
2
Tools for functional genetic analyses in lamprey are not as well developed as in other SCI models.
3
The study used an inhibitor that targets secretion of all Wnts, so the precise components of this pathway needed to support regeneration after SCI requires further inquiry.

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