8/18/2023 0 Comments Neurite dendrite axon![]() In addition to triggering regeneration from a dendrite, injury of the axon close to the cell body has the potential to induce formation of multiple axons. This type of regeneration is therefore broadly conserved. More recently, regeneration of an axon from a dendrite was shown to occur after proximal axotomy in Drosophila sensory neurons. Hippocampal neurons in dissociated and slice culture initiate growth of an axon from a dendrite after proximal axotomy, and in this case the new axon was shown to be able to form synapses. Retinal ganglion cells in hamster and spinal neurons in rats also respond to proximal axotomy by sprouting axons from dendrites. Axon-like processes (ALPs) emerging from distal tips of dendrites after proximal axotomy have been reported in adult feline motoneurons and interneurons. Similar observations have been made in mammalian neurons. This was first described in reticulospinal neurons of the sea lamprey, a jawless fish, where axon removal resulted in extensive sprouting from dendrites, and the ultrastructure of these sprouts resembled that of axons. While regeneration from a remaining stump is the most commonly studied type of axon regeneration, in many systems when the axon is severed very close to the cell body (proximal axotomy) a new axonal process arises from the dendrites rather than the cell body or short axon stump. 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. 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, interneurons in snails, motor neurons in C.elegans and Drosophila and sensory neurons in C. In some cases, particularly in the peripheral nervous system, regrowing axons may ultimately reconnect with targets to recover function. 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. MethodsÄrosophila 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. ![]()
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