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.
Digital Object Identifier (DOI)
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.
Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-017-18757-1.
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.
41598_2017_18757_MOESM2_ESM.xlsx (24030 kB)
Supplementary Table S1
41598_2017_18757_MOESM3_ESM.xlsx (50 kB)
Supplemental Table S2
41598_2017_18757_MOESM4_ESM.xlsx (373 kB)
Supplemental Table S3
41598_2017_18757_MOESM5_ESM.xlsx (45 kB)
Supplemental Table S4
41598_2017_18757_MOESM6_ESM.xlsx (21 kB)
Supplemental Table S5
41598_2017_18757_MOESM7_ESM.xlsx (563 kB)
Supplemental Table S6
41598_2017_18757_MOESM8_ESM.xlsx (15 kB)
Supplemental Table S7
41598_2017_18757_MOESM9_ESM.mp4 (32605 kB)