Different responses to spinal cord injury (SCI) in zebrafish and mammals. Representation of different cellular events occurring after SCI in zebrafish and mice. Upon SCI in mammals, a complex cascade of events occurs, leading to the formation of a scar at the lesion site constructed by stromal-derived fibroblasts, inflammatory immune cells and hypertrophic astrocytes. The scar impedes the regrowth of spared axons. Conversely, in zebrafish, injury induces the infiltration of immune cells followed by bridging of glial cells and axonal tracts, leading to functional regeneration.

Time course of spinal cord regeneration in zebrafish. (Top) In zebrafish larvae, spinal cord transection destroys axonal and glial connections, eliciting the formation of a tissue bridge that spans the injury epicenter by 2 days post-injury (dpi). A remodeling phase follows at 3 dpi. (Bottom) A similar response to injury is observed in adult zebrafish. By 15 dpi, some axonal and glial processes have traversed the injury site. Subsequent remodeling reconstitutes structure.

ERG progenitor subpopulations. A cross section of the spinal cord, illustrating the proposed ERGs organized in compartments that give rise to different neuron types. Transcription factors in the gray zones are common to all ERGs. Pax6- and Nkx6.1-expressing ERGs (yellow zones) give rise to V2 interneurons, ERGs expressing Pax6, Nkx6.1 and Olig2 (red zones) give rise to motor neurons, and ERGs only expressing Nkx6.1 (green zones) give rise to serotonergic neurons.

Signals inducing neurogenesis, glial bridging and axon regrowth after SCI. Several signaling factors have been implicated in the regrowth of axons (Syntenin-a, L1.1, Sema4d), neurogenesis (dopamine, Notch, Hh, Fgf), and formation of a glial bridge (Ctgf, Fgf) after SCI in zebrafish. For some of these (i.e. dopamine, Notch, Fgf), unexpected similarities can be observed among vertebrates with different capacities for spinal cord regeneration.