Synaptic organization in health and disease

Netrin and its receptor DCC are best known for their roles in axon guidance during neural development. However, recent work from our group and others has revealed additional functions for this pathway in synapse formation and maintenance. We showed that in C. elegans, the netrin receptor DCC/UNC-40 is dynamically regulated through ubiquitin-mediated protein degradation, and that this regulation controls the stability of synaptic connections. Building on this discovery, we are now investigating how DCC-dependent synapse stabilization influences neuronal health. By combining studies in C. elegans, mouse models, and human neuronal cultures, we aim to understand how dysregulation of this conserved pathway affects the maintenance and vulnerability of the adult nervous system.