Neuronal morphogenesis in Drosophila

The Rumpf lab uses Drosophila to study the processes that determine the morphology of axons and dendrites during development. Due to their well-established genetics and short life cycle (see schematic), flies are an ideal model organism in developmental biology. Our favourite model neurons are „class IV dendritic arborization“ (c4da) neurons, peripheral sensory neurons located in the skin of Drosophila larvae. Their axons and dendrites can be easily visualized by expression of fluorescent markers. The big picture above (by Sandra Rode & Svende Herzmann) is a whole-mount Drosophila larva expressing Green Fluorescent Protein (GFP) specifically in c4da neurons.

Not only outgrowth of neuronal processes, but also regressive events are important for a neuron to reach its mature morphology during development. Retraction or degeneration of axons and dendrites without loss of the cell body are collectively referred to as „pruning“. C4da neurons specifically prune their larval dendrites at the onset of the pupal phase (see movie). C4da neuron dendrite pruning is induced by the steroid hormone ecdysone and involves the local degeneration of the larval dendrites. Dendrite pruning is a stunning example of spatial regulation: in the dendrites, the cytoskeleton is locally destroyed, and the plasma membrane is precisely cut at a predetermined break site. All the while, the cytoskeleton and membrane of the cell body and axon are maintained and remain untouched.

The Ubiquitin-Proteasome System

Protein degradation through the ubiquitin-proteasome system (UPS) is required for dendrite pruning. In this system, proteins destined for degradation are marked by covalent attachment of the small protein ubiquitin (or chains of ubiquitin). Such "ubiquitylated" proteins are then recognized by the proteasome (a large protease) and degraded. We have recently shown that „Valosin-Containing Protein“ (VCP), a ubiquitin-dependent chaperone and UPS component, is required for dendrite pruning. Interestingly, VCP is required for the correct expression of an ecdysone-induced gene (Rumpf, 2014). We use fly genetics, live imaging and biochemistry to figure out how VCP and other UPS components are required for pruning.