Oriented growth of regenerating axons in axolotl forelimbs is consistent with guidance by diffusible factors from distal nerve stumps.

Previous studies have shown that when peripheral nerves in axolotl limbs are cut and surgically misdirected, regenerating axons grow back to the original pathways and innervate their correct muscles. In the present study however, we demonstrate that when given a choice between their correct nerve stump and an incorrect stump (forearm flexor nerve), regenerating extensor cranialis nerve axons grow towards both pathways. This result suggests that the directed growth of regenerating axons in the peripheral nervous system may be in response to factor(s) released from the distal nerve stumps, but that in this region of the limb, axons were unable to differentiate between correct and incorrect pathways. Growing axons appeared to be accompanied by neural sheath cells, whilst activated macrophages remained near the cut nerve stumps. Possible mechanisms by which regenerating axons may eventually innervate their correct targets are discussed.