We study how the nervous system of the fruit fly is ‘wired together’ during development. By exploiting the extreme biology of metamorphosis, we have been able to uncover novel cellular and molecular mechanisms of neurodevelopment.
Pruning is the selective elimination of synapses, axons or dendrites and is essential for the refinement of circuits. Pruning is found throughout the animal kingdom and its dysregulation in humans is believed to underlie a number of developmental disorders. Large-scale pruning involves the removal of relatively long neuronal processes and takes place by a local degeneration. At present we still know little about the mechanisms that orchestrate branch-specific auto-destruction events. We take advantage of the small number of sensory neurons that undergo a dramatic remodeling during metamorphosis. We have developed imaging techniques that allow us to see this phenomenon live in intact animals. Using fly genetics we found that the caspases, cysteine proteases synonymous with apoptosis, are activated locally within the dendritic compartment of pruning sensory neurons, but not in the soma or axon. We have also recently shown that a subset of ESCRT proteins are required for the scission event that takes place during branch severing. Our long-term goal is to understand the molecular machineries that orchestrate this program. Specifically, we would like to know how the neuronal cytoskeleton is remodeled in branches, how those branches are then cut away from the parent neuron and how they are then cleared.