Grant: Operating Grant

Neurons have complex architectures that change with time. Most neurons initially produce extensive and elaborate processes that are subsequently pruned so that only those that are used to mediate neuron-neuron and neuron-target communication, and thus form part of a neuronal network, are retained. After injury, damaged neuronal processes can be removed, also through activation of these pruning mechanisms. The goal of this proposal is to understand how this intrinsic self-destruct program becomes activated within developing neurons. We know that process has to be exquisitely well controlled for it to selectively prune processes in the nervous system but the means by which it is activated obscure. This research program will identify cellular mechanisms that allow neurons to destroy their own neurites. We believe this is important because emerging evidence indicates that inappropriate re-activation of this degenerative program is an early event in several forms of neurodegenerative disease. This study will provide new insights into the fundamental signaling and regulatory mechanisms that regulate neurite destruction and may identify therapeutic opportunities to slow neurodegenerative disorders.