Remodeling replaces cut axons

Neurons in the fly can radically remold their cytoskeleton to rebuild a severed axon -- a finding that might provide clues to how neurons recover from injury, researchers reported yesterday at the American Society for Cell Biology meeting in San Diego. Image: Wikipedia To rebuild the severed axon, neurons in the fly ramp up their production of microtubules -- the main structural elements of the cytoskeleton -- and recreate the microtubules characteristic of the axon in a nearby part of the ce

Written byAlla Katsnelson

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Image: Wikipedia

To rebuild the severed axon, neurons in the fly ramp up their production of microtubules -- the main structural elements of the cytoskeleton -- and recreate the microtubules characteristic of the axon in a nearby part of the cell. Neurons are strongly polarized cells: a neuron's single axon transmits information, while its multitude of branches, or dendrites, receive information, either in the form of electrical signals from the axons of other nearby neurons, or from input such as a touch to the skin, or other sensory or mechanical stimulation. Without an axon, the cell's chief output organ, the cell will die. One element maintaining their polarity linkurl:appears to be the direction;https://www.molbiolcell.org/cgi/content/abstract/19/10/4122 in which the microtubules, which transport proteins throughout the cell, are stacked. In axons, virtually all microtubules are positioned to transport proteins away from the cell body, while in dendrites, about 90% are oriented in the opposite direction. Researchers have previously noted changes in the shape of neurons after axons are cut, and "have seen things growing out of dendrites," linkurl: Melissa Rolls;https://www.bmb.psu.edu/faculty/rolls/rolls.html of Penn State University, the principal investigator on the project, told The Scientist. Those new protrusions "looked like axons," she explained, but nobody had ever looked under the hood, as it were, to characterize the cells' reorganization and what's causing it. Michelle Stone, a graduate student in Rolls's lab, took a closer look at what happened to the polarity of microtubules during this process. In sensory neurons of whole, living Drosophila larvae, Stone cut the axons with a laser, then used live cell imaging to track the microtubule protein EB1, marked with GFP. To their surprise, the researchers saw a huge surge in the number of microtubules moving throughout the cytoplasm, with the EB1-GFP imaging showing the dynamic microtubules "swirling" in the cell body and traveling in different directions in dendrites. After 48 hours, the cytoskeletal disturbance began to settle down, with one dendrite in the injured neuron having rebuilt its microtubule structure to the "send-out" polarity normally characteristic of axons. The researchers didn't see that pattern when dendrites were cut. It's not clear whether the rebuilt axon reaches its target and functions, though Rolls suspects in this case it won't. Past studies on other organisms suggest that axons only continue to function if they are cut further away from the cell body than in the current experiment. The group is now looking at whether they get the same switch in dendrite polarity with more distal axonal cuts in their model, she said. Researchers have struggled to understand basic features of neuronal polarity, said linkurl:Ron Dubreuil,;https://www.uic.edu/depts/bios/faculty/dubreuil/dubreuil.shtml who studies cytoskeletal proteins at the University of Illinois in Chicago and saw Stone's presentation, but this work is an exception. "It's a case where you need a breakthrough," Dubreuil said of the field, "and this [study] is an example of that," in its demonstration that microtubules can respond so dynamically to change their polarity. "What these cells do is dissolve the inside of the cell and rebuild the axon," said Rolls in a later press briefing. Rolls and Stone hope to "figure out what's going on inside these cells, so we can tap into that capacity [to spur regeneration] in higher organisms," Rolls said.
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[18th January 2005]