Normal Spastin Gene Dosage Is Specifically Required for Axon Regeneration

Michelle C. Stone, Kavitha Rao, Kyle W. Gheres, Seahee Kim, Juan Tao, Caroline La Rochelle, Christin T. Folker, Nina T. Sherwood, Melissa M. Rolls

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Axon regeneration allows neurons to repair circuits after trauma; however, most of the molecular players in this process remain to be identified. Given that microtubule rearrangements have been observed in injured neurons, we tested whether microtubule-severing proteins might play a role in axon regeneration. We found that axon regeneration is extremely sensitive to levels of the microtubule-severing protein spastin. Although microtubule behavior in uninjured neurons was not perturbed in animals heterozygous for a spastin null allele, axon regeneration was severely disrupted in this background. Two types of axon regeneration-regeneration of an axon from a dendrite after proximal axotomy and regeneration of an axon from the stump after distal axotomy-were defective in Drosophila with one mutant copy of the spastin gene. Other types of axon and dendrite outgrowth, including regrowth of dendrites after pruning, were normal in heterozygotes. We conclude that regenerative axon growth is uniquely sensitive to spastin gene dosage.

Original languageEnglish (US)
Pages (from-to)1340-1350
Number of pages11
JournalCell Reports
Volume2
Issue number5
DOIs
StatePublished - Nov 29 2012

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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