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Wheeler, M. K.

Publications and source records attributed to Wheeler, M. K..

2 recordsLinked to original sources

Transcriptomic analysis identifies injury-responsive fibroblast populations as potential mediators of Wnt-dependent spinal cord regeneration

BackgroundIn humans and other mammals, spinal cord injury (SCI) can lead to a permanent loss of sensory and motor function, due to the inability of damaged neurons and axons to regenerate. However, other vertebrate species including zebrafish exhibit complete spinal cord regeneration and functional recovery after SCI. Wnt signaling is required for neurogenesis and axon regrowth in a larval zebrafish SCI model, but the genes regulated by this pathway and the cell types that express them remain largely unknown. ResultsIn this study, we used bulk RNA-sequencing (RNAseq) to identify candidate genes regulated by Wnt signaling that are expressed after SCI. Using this unbiased screen, we identified multiple genes previously unassociated with SCI in larval zebrafish, and confirmed by in situ hybridization that their expression is injury-responsive, Wnt-dependent, and localized to fibroblast-like cells surrounding the spinal cord. ConclusionsTogether, our data reveal potential novel gene targets and cell populations that may play important roles in spinal cord regeneration.

developmental biology↗

Regenerated Interneurons Integrate Into Locomotor Circuitry Following Spinal Cord Injury

Whereas humans and other adult mammals lack the ability to regain locomotor function after spinal cord injury, zebrafish are able to recover swimming behavior even after complete spinal cord transection. We have previously shown that zebrafish larvae regenerate lost neurons within 9 days post-injury (dpi), but the functional contribution of these neurons to motor recovery is unknown. Here we show that multiple interneuron subtypes known to play a role in locomotor circuitry are regenerated in injured spinal cord segments during the period of functional recovery. Further, we show that one subtype of newly-generated interneurons receives excitatory input and fires synchronously with motor output by 9 dpi. Taken together, our data show that regenerative neurogenesis in the zebrafish spinal cord produces interneurons with the physiological capacity to participate in the recovery of locomotor function.

neuroscience↗