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.
Highlights
A fundamental question in regenerative biology is why some organisms can regenerate their central nervous system (CNS), while others cannot[1]
We identified complex transcriptional responses in both spinal cord and brain throughout the 12 weeks after injury, including a number of expression changes mapping to the Wnt pathway, and used pharmacological blockade of Wnt signaling to demonstrate its critical importance in functional recovery
The lamprey CNS contains many homologous structures that are shared with mammals, including a tripartite brain and spinal cord with motor and sensory circuits (Fig. 1a)[14,21,22,23]
Summary
A fundamental question in regenerative biology is why some organisms can regenerate their central nervous system (CNS), while others cannot[1]. The lamprey is a member of an ancient vertebrate lineage that diverged from a common ancestor of humans ~550 million years ago[11,12,13] Despite this evolutionary distance, recent sequencing of the lamprey genome revealed molecular pathways that are conserved with mammals, including genes related to axon guidance and regeneration, synaptic transmission, neural patterning and neurodegeneration[12]. To better understand the molecular pathways supporting successful functional recovery, we used RNA-Seq to determine transcriptional profiles in spinal cord of lampreys after SCI. We identified complex transcriptional responses in both spinal cord and brain throughout the 12 weeks after injury, including a number of expression changes mapping to the Wnt pathway, and used pharmacological blockade of Wnt signaling to demonstrate its critical importance in functional recovery
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
