The mechanisms underlying the inability of CNS axons to regenerate after injury are incompletely understood. Here, Delpech et al. show that long-distance regeneration of damaged retinal ganglion cell (RGC) axons and reinnervation of a functional circuit can be achieved in mice by inhibiting SLIT–ROBO repulsive signalling.

The authors used the optic nerve-crush injury (ONC) model, in which RGC axons are damaged, disrupting the relay of visual information from RGCs to the suprachiasmatic nucleus (SCN) — the ‘master regulator’ of circadian rhythms. Following ONC, co-activation of specific signalling pathways enables RGC axons to regenerate and reach the SCN, but they do not enter the nucleus. The authors reasoned that the expression of developmental axon-guidance cues in the mature nervous system might account for the axons’ avoidance of the SCN.