Establishment of a novel axon pruning model of Drosophila motor neuron

Abstract

ABSTRACT Developmental neuronal pruning is a process by which neurons selectively remove excessive or unnecessary neurite without causing neuronal death. Importantly, this process is widely used for the refinement of neural circuits in both vertebrates and invertebrates, and may also contribute to the pathogenesis of neuropsychiatric disorders, such as autism and schizophrenia. In the peripheral nervous system (PNS), class IV dendritic arborization (da) sensory neurons of Drosophila, selectively remove the dendrites without losing their somas and axons, while the dendrites and axons of mushroom body (MB) γ neuron in the central nervous system (CNS) are eliminated by localized fragmentation during metamorphosis. Alternatively, dendrite pruning of ddaC neurons is usually investigated via live-cell imaging, while dissection and fixation are currently used for evaluating MB γ neuron axon pruning. Thus, an excellent model system to assess axon specific pruning directly via live-cell imaging remains elusive. Here, we report that the Drosophila motor neuron offers a unique advantage for studying axon pruning. Interestingly, we uncover that long-range projecting axon bundle from soma at ventral nerve cord (VNC), undergoes degeneration rather than retraction during metamorphosis. Strikingly, the pruning process of the motor axon bundle is straightforward to investigate via live imaging and it occurs approximately at 22 h after pupal formation (APF), when axon bundles are completely cleared. Consistently, the classical axon pruning regulators in the Drosophila MB γ neuron, including TGF-β signaling, ecdysone signaling, JNK signaling, and the ubiquitin-proteasome system are also involved in governing motor axon pruning. Finally, our findings establish an unprecedented axon pruning mode that will serve to systematically screen and identify undiscovered axon pruning regulators. This article has an associated First Person interview with the first author of the paper.