GSBS Student Publications
Title
dSarm/Sarm1 is required for activation of an injury-induced axon death pathway
GSBS Program
Neuroscience
UMMS Affiliation
Department of Neurobiology; Department of Neurology; Freeman Lab; Graduate School of Biomedical Sciences, Neuroscience Program; Graduate School of Biomedical Sciences, MD/PhD Program
Date
7-27-2012
Document Type
Article
Medical Subject Headings
Animals; Animals, Genetically Modified; Apoptosis; Armadillo Domain Proteins; Axons; Axotomy; Cell Survival; Cells, Cultured; Cytoskeletal Proteins; Denervation; Drosophila; Drosophila Proteins; Mice; Mutation; Neurons; Sciatic Nerve; Signal Transduction; Superior Cervical Ganglion; Tissue Culture Techniques; *Wallerian Degeneration
Disciplines
Neuroscience and Neurobiology
Abstract
Axonal and synaptic degeneration is a hallmark of peripheral neuropathy, brain injury, and neurodegenerative disease. Axonal degeneration has been proposed to be mediated by an active autodestruction program, akin to apoptotic cell death; however, loss-of-function mutations capable of potently blocking axon self-destruction have not been described. Here, we show that loss of the Drosophila Toll receptor adaptor dSarm (sterile alpha/Armadillo/Toll-Interleukin receptor homology domain protein) cell-autonomously suppresses Wallerian degeneration for weeks after axotomy. Severed mouse Sarm1 null axons exhibit remarkable long-term survival both in vivo and in vitro, indicating that Sarm1 prodegenerative signaling is conserved in mammals. Our results provide direct evidence that axons actively promote their own destruction after injury and identify dSarm/Sarm1 as a member of an ancient axon death signaling pathway.
Related Resources
Journal Title
Science (New York, N.Y.)
PubMed ID
22678360
Repository Citation
Osterloh, Jeannette M.; Yang, Jing; Rooney, Timothy M.; Fox, A. Nicole; Adalbert, Robert; Powell, Eric H.; Sheehan, Amy E.; Avery, Michelle A.; Hackett, Rachel; Logan, Mary A.; MacDonald, Jennifer M.; Ziegenfuss, Jennifer S.; Milde, Stefan; Hou, Ying-Ju; Nathan, Carl; Ding, Aihao; Brown, Robert H. Jr.; Comforti, Laura; Coleman, Michael; Tessier-Lavigne, Marc; Zuchner, Stephan; and Freeman, Marc R., "dSarm/Sarm1 is required for activation of an injury-induced axon death pathway" (2012). GSBS Student Publications. 1789.
https://escholarship.umassmed.edu/gsbs_sp/1789
Comments
Citation: Science. 2012 Jul 27;337(6093):481-4. Epub 2012 Jun 7. Link to article on publisher's site