dSarm/Sarm1 is required for activation of an injury-induced axon death pathway

Jeannette M. Osterloh, Jing Yang, Timothy M. Rooney, A. Nicole Fox, Robert Adalbert, Eric H. Powell, Amy E. Sheehan, Michelle A. Avery, Rachel Hackett, Mary A. Logan, Jennifer M. MacDonald, Jennifer S. Ziegenfuss, Stefan Milde, Ying Ju Hou, Carl Nathan, Aihao Ding, Robert H. Brown, Laura Conforti, Michael Coleman, Marc Tessier-LavigneStephan Züchner, Marc R. Freeman

Research output: Contribution to journalArticle

254 Scopus citations

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 a/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 amember of an ancient axon death signaling pathway.

Original languageEnglish (US)
Pages (from-to)481-484
Number of pages4
JournalScience
Volume337
Issue number6093
DOIs
StatePublished - Jul 27 2012

ASJC Scopus subject areas

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    Osterloh, J. M., Yang, J., Rooney, T. M., Fox, A. N., Adalbert, R., Powell, E. H., Sheehan, A. E., Avery, M. A., Hackett, R., Logan, M. A., MacDonald, J. M., Ziegenfuss, J. S., Milde, S., Hou, Y. J., Nathan, C., Ding, A., Brown, R. H., Conforti, L., Coleman, M., ... Freeman, M. R. (2012). dSarm/Sarm1 is required for activation of an injury-induced axon death pathway. Science, 337(6093), 481-484. https://doi.org/10.1126/science.1223899