Article abstract
Nature Neuroscience 11, 649 - 658 (2008)
Published online: 1 April 2008 | doi:10.1038/nn.2114
Developmental axon pruning mediated by BDNF-p75NTR–dependent axon degeneration
Karun K Singh1,2,8, Katya J Park1,2,3, Elizabeth J Hong4,5, Bianca M Kramer1,2, Michael E Greenberg4,5, David R Kaplan2,3,6 & Freda D Miller1,2,6,7
Abstract
The mechanisms that regulate the pruning of mammalian axons are just now being elucidated. Here, we describe a mechanism by which, during developmental sympathetic axon competition, winning axons secrete brain-derived neurotrophic factor (BDNF) in an activity-dependent fashion, which binds to the p75 neurotrophin receptor (p75NTR) on losing axons to cause their degeneration and, ultimately, axon pruning. Specifically, we found that pruning of rat and mouse sympathetic axons that project to the eye requires both activity-dependent BDNF and p75NTR. p75NTR and BDNF are also essential for activity-dependent axon pruning in culture, where they mediate pruning by directly causing axon degeneration. p75NTR, which is enriched in losing axons, causes axonal degeneration by suppressing TrkA-mediated signaling that is essential for axonal maintenance. These data provide a mechanism that explains how active axons can eliminate less-active, competing axons during developmental pruning by directly promoting p75NTR-mediated axonal degeneration.
- Developmental and Stem Cell Biology, Hospital for Sick Children, 555 University Avenue, Toronto, Canada M5G 1X8.
- Institute of Medical Science, University of Toronto, Medical Sciences Building, Toronto, Ontario, Canada M5S 1A8.
- Cell Biology Group, Hospital for Sick Children, 555 University Avenue, Toronto, Canada, M5G 1X8.
- Children's Hospital Boston, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
- Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA.
- Departments of Molecular and Medical Genetics, University of Toronto, Medical Sciences Building, Toronto, Ontario, Canada M5S 1A8.
- Department of Physiology, University of Toronto, Medical Sciences Building, Toronto, Ontario, Canada M5S 1A8.
- Present address: Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Building 46-4223, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Correspondence to: Freda D Miller1,2,6,7 e-mail: fredam@sickkids.ca
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