After being severed from the cell body, axons initiate an active degeneration program known as Wallerian degeneration. Although dendrites also seem to have an active injury-induced degeneration program, no endogenous regulators of this process are known. Because microtubule disassembly has been proposed to play a role in both pruning and injury-induced degeneration, we used a Drosophila model to identify microtubule regulators involved in dendrite degeneration. We found that, when levels of fidgetin were reduced using mutant or RNA interference (RNAi) strategies, dendrite degeneration was delayed, but axon degeneration and dendrite pruning proceeded with normal timing. We explored two possible ways in which fidgetin could promote dendrite degeneration: (1) by acting constitutively to moderate microtubule stability in dendrites, or (2) by acting specifically after injury to disassemble microtubules. When comparing microtubule dynamics and stability in uninjured neurons with and without fidgetin, we could not find evidence that fidgetin regulated microtubule stability constitutively. However, we identified a fidgetin-dependent increase in microtubule dynamics in severed dendrites. We conclude that fidgetin acts after injury to promote disassembly of microtubules in dendrites severed from the cell body.
The authors declare no competing or financial interests.
J.T. and C.F. designed and performed experiments and analyzed data. M.M.R. supervised experiments and wrote the manuscript.
Funding was provided by the National Institutes of Health [grant number R01GM085115] and the Pew Charitable Trusts; M.M.R. was a Pew Scholar in the Biomedical Sciences. Deposited in PMC for release after 12 months.
Supplementary information available online at http://jcs.biologists.org/lookup/doi/10.1242/jcs.188540.supplemental
- Received February 25, 2016.
- Accepted July 8, 2016.
- © 2016. Published by The Company of Biologists Ltd