Project B04

Membrane Remodeling and Severing During Dendrite Pruning in Drosophila Neurons

Neuronal morphogenesis and circuit formation involve both progressive events like growth of axons and dendrites, and regressive events such as elimination or degeneration of synapses or sometimes long stretches of neurites, collectively known as pruning. The rearrangement of cellular membranes and membrane interfaces is an important but little-understood aspect of pruning. Peripheral sensory neurons of Drosophila larvae prune their extensive larval dendrites at the onset of metamorphosis in an ecdysone-dependent manner through a degenerative mechanism. Dendrite pruning requires the loss of cell adhesion molecules (CAMs). The molecular mechanisms underlying CAM degradation are not well understood, and it is not clear which specific cellular interfaces must be remodeled to allow pruning, or how lack of interface remodeling interferes with dendrite pruning. We have identified membrane trafficking regulators required for pruning and CAM degradation. We propose to use these mutants to unravel the triggers and mechanisms of CAM degradation, to identify the affected membrane interfaces, and to identify the mechanisms by which interface remodeling contributes to pruning.