2008 Brain Star Award Recipient - Karun Singh
Recipient
Karun Singh - Biosketch
PhD
University of Toronto
Article
Karun K Singh, Katya J Park, Elizabeth J Hong, Bianca M Kramer, Michael E Greenberg, David R Kaplan, Freda D Miller. Developmental axon pruning mediated by BDNF-p75NTR–dependent axon degeneration: NATURE NEUROSCIENCE (advance online publication). Published online 1 April 2008; doi:10.1038/nn.2114.
Significance of the paper
During development of the mammalian nervous system, there are an excess number of nerve projections (axons) that are produced which will ultimately make a limited number of connections with target organs. In order to establish a functional nervous system, this surplus of axons are eliminated through a competitive process termed "axon pruning". A key question in neurobiology is how does this process occur?
In the present study, we have investigated the molecular signals that regulate this event.Using sympathetic neurons which project to the eye as a model system, we determined that Brain-derived neurotrophic factor (BDNF) is secreted in a neural activity-dependent fashion from successful axons, binds to the p75 neurotrophin receptor (p75NTR) on unsuccessful axons terminals and causes axon degeneration. Furthermore, we found that this BDNF-p75NTR signal elicited axon degeneration by suppressing a major positive growth signal which axons require to grow and connect with their targets. These results suggest a mechanism for developmental axon elimination whereby axons that successfully make functions connections secrete BDNF, which binds p75NTR on unsuccessful, losing axons, causing them to degenerate.
The significance of our findings was highlighted by a Nature Neuroscience "News and Views" article which commented on our and another group's recent publication which revealed a similar mechanism also regulates naturally occurring apoptosis (cell death) of developing sympathetic neurons. This work suggests that a BDNF-p75NTR signaling cascade may be a general mechanism for eliminating unnecessary neurons and axons during development.