Abstract
In mammals, spinal cord injury (SCI) leads to dramatic losses in neurons and synaptic connections, and consequently function. 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 performed RNA-Seq on lamprey spinal cord and brain throughout the course of functional recovery. 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. Furthermore, a number of highly conserved axon guidance, extracellular matrix, and proliferation genes were also differentially expressed after SCI in lampreys. Strikingly, ~3% of differentially expressed transcripts belonged to the Wnt pathways. These included members of the Wnt and Frizzled gene families, and genes involved in downstream signaling. 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.
Document Type
Article
Publication Date
1-15-2018
Digital Object Identifier (DOI)
https://doi.org/10.1038/s41598-017-18757-1
Funding Information
We gratefully acknowledge support from the National Institutes of Health (R03NS078519 to OB; R01GM104123 to JJS; R01NS078165 to JRM), The Feinstein Institute for Medical Research and The Marine Biological Laboratory, including the Charles Evans Foundation Research Award, the Albert and Ellen Grass Foundation Faculty Research Award, and The Eugene and Millicent Bell Fellowship Fund in Tissue Engineering.
Related Content
Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-017-18757-1.
Repository Citation
Herman, Paige E.; Papatheodorou, Angelos; Bryant, Stephanie A.; Waterbury, Courtney K. M.; Herdy, Joseph R.; Arcese, Anthony A.; Buxbaum, Joseph D.; Smith, Jeramiah J.; Morgan, Jennifer R.; and Bloom, Ona, "Highly Conserved Molecular Pathways, Including Wnt Signaling, Promote Functional Recovery From Spinal Cord Injury in Lampreys" (2018). Biology Faculty Publications. 155.
https://uknowledge.uky.edu/biology_facpub/155
Supplemental Information
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Supplementary Video
Notes/Citation Information
Published in Scientific Reports, v. 8, article no. 742, p. 1-15.
© The Author(s) 2018
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