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.

Pruning Pathways: Cytoskeleton, Metabolism and UPS

Neurite pruning requires the cooperation of many cellular pathways. The dendritic "plus-end in" organization of microtubules is a prerequisite for their disassembly through alterations in microtubule dynamics (Herzmann, 2017, 2018). While growth pathways are suppressed, mitochondria must still provide sufficient energy to produce pruning factors (Marzano, 2021), and the ubiquitin-proteasome system (UPS) is also required for the correct expression of an ecdysone-induced gene (Rumpf, 2014). While most of these pathways act in c4da neurons, dendrite severing requires mechanical forces from surrounding tissues (Krämer, Wolterhoff, 2023) The TOR pathway, on the other hand, speeds up protein production for dendrite regrowth after pruning (Sanal, 2023). We use fly genetics, sophisticated live imaging techniques and biochemistry to figure out how these remodeling pathways work.