Classic axon regeneration involves signaling from the site of injury back to the cell body, followed by initiation of outgrowth from the remaining axon stump.

In response to axon severing, many neurons have the capacity to regenerate this part of the cell. We conclude that both ddaE and ddaC can regenerate axons either from the stump or a dendrite, and that there is some feedback between the two sites that modulates dendritic microtubule polarity. However, changes in dendritic microtubule polarity differed in response to the two types of injury, and were influenced by the presence of a scar at the distal axotomy site. A transcriptional reporter for axon injury signaling, puc-GFP, increased with similar timing and levels after proximal and distal axotomy. Because cutting the axon close to the cell body results in growth of the new axon from a dendrite, and cutting further out may not, we asked whether the initial response in the cell body was similar after both types of injury. We next demonstrated if a stump remains, new axons can originate from this site and a dendrite at the same time. We also showed that ddaC neurons regenerate from the dendrite when the axon is severed close to the cell body. We found that ddaE neurons can initiate regeneration from an axon stump when a stump remains. To provide a more complete picture of axon regeneration in these cell types, we performed additional injury types. In Drosophila, it has been shown that a complex sensory neuron, ddaC, can regenerate an axon from a stump, and a simple sensory neuron, ddaE, can regenerate an axon from a dendrite. Methodsĭrosophila sensory neurons are ideal for studying neuronal injury responses because they can be injured reproducibly in a variety of genetic backgrounds. However, in many mammalian neurons, new axons initiate from a dendritic site when the axon is injured close to the cell body. New outgrowth often originates from the remaining axon stump. After axon severing, neurons recover function by reinitiating axon outgrowth.

Axon to dendrite to cellbody