Abstract
BackgroundAfter axon severing, neurons recover function by reinitiating axon outgrowth. New outgrowth often originates from the remaining axon stump. However, in many mammalian neurons, new axons initiate from a dendritic site when the axon is injured close to the cell body.MethodsDrosophila sensory neurons are ideal for studying neuronal injury responses because they can be injured reproducibly in a variety of genetic backgrounds. 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. To provide a more complete picture of axon regeneration in these cell types, we performed additional injury types.ResultsWe found that ddaE neurons can initiate regeneration from an axon stump when a stump remains. We also showed that ddaC neurons regenerate from the dendrite when the axon is severed close to the cell body. We next demonstrated if a stump remains, new axons can originate from this site and a dendrite at the same time. 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. A transcriptional reporter for axon injury signaling, puc-GFP, increased with similar timing and levels after proximal and distal axotomy. 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.ConclusionsWe 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.
Highlights
IntroductionNeurons recover function by reinitiating axon outgrowth
After axon severing, neurons recover function by reinitiating axon outgrowth
Initiation of regeneration from a remaining axon stump has been observed in many types of neurons in vivo, including interneurons in the mouse spinal cord [4], interneurons in snails [5], motor neurons in C.elegans [6] and Drosophila [7] and sensory neurons in C. elegans [8] and Drosophila [9]
Summary
Neurons recover function by reinitiating axon outgrowth. In many mammalian neurons, new axons initiate from a dendritic site when the axon is injured close to the cell body. In response to axon severing, many neurons have the capacity to regenerate this part of the cell. 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 [1,2,3]. Initiation of regeneration from a remaining axon stump has been observed in many types of neurons in vivo, including interneurons in the mouse spinal cord [4], interneurons in snails [5], motor neurons in C.elegans [6] and Drosophila [7] and sensory neurons in C. elegans [8] and Drosophila [9]. It is likely that in all of these scenarios an initial MAP kinase signaling cascade that includes Dual Leucine Zipper Kinase (DLK) is required to initiate regeneration, as it has been shown to be central in all cases where it has been tested [6, 7, 10, 11].
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