Progenitor derived glia are required for spinal cord regeneration in zebrafish

Abstract

Unlike mammals, adult zebrafish undergo spontaneous recovery after major spinal cord injury. Whereas reactive gliosis presents a roadblock for mammalian spinal cord repair, glial cells in zebrafish elicit pro-regenerative bridging functions after injury. Here, we perform genetic lineage tracing, assessment of regulatory sequences, and inducible cell ablation to define mechanisms that direct the molecular and cellular responses of glial cells after spinal cord injury in adult zebrafish. Using a newly generated CreERT2 transgenic line, we show that cells that direct expression of the bridging glial marker ctgfa give rise to regenerating glia after injury, with negligible contribution to either neuronal or oligodendrocyte lineages. A 1 kb sequence upstream of the ctgfa gene was sufficient to direct expression in early bridging glia after injury. Finally, ablation of ctgfa-expressing cells using a transgenic nitroreductase strategy impaired glial bridging and recovery of swim behavior after injury. This study identifies key regulatory features, cellular progeny, and requirements of glial cells during innate spinal cord regeneration.

Differential roles of diet on development and spinal cord regeneration in larval zebrafish

“…1C,D) with only a 16% increase in body length during recovery suggesting that resources are prioritized towards regeneration over growth after an injury in larval zebrafish. Consistent with previous studies, (26,31,32) larval zebrafish began the formation of a glial bridge 2-3 days post-injury (dpi) with 74% of larvae forming a glial bridge at 5 dpi (Table 1). As growth after transection was less than that seen during normal development, we next tracked survival (Fig.…”

“…This line labels radial glial, which form a pro-regenerative glial bridge after SCI. (26)(27)(28)(29)(30)(31) After transection, zebrafish exhibited limited growth (Fig. 1C,D) with only a 16% increase in body length during recovery suggesting that resources are prioritized towards regeneration over growth after an injury in larval zebrafish.…”