Axonal death 3: Axon death from a fly’s perspective
Axon degeneration is a shared feature in neurodegenerative disease, and when nervous systems are challenged by mechanical or chemical forces. Yet our understanding of the molecular mechanisms underlying axon degeneration remains fairly limited. Injury-induced axon degeneration serves as a simple model to study how severed axons execute their own disassembly. Discovered by and named after Augustus Waller in 1850, Wallerian degeneration is an umbrella term that comprises of two distinct, molecularly separable processes. First, after axonal injury, axons separated from their cell bodies actively execute their own self-destruction (axon death) through an evolutionarily conserved axon death signaling cascade within one day after injury. Second, surrounding glia and specialized phagocytes engage and clear the resulting axonal debris within three to five days. Over recent years, an evolutionarily conserved axon death signaling cascade has been identified from flies to mammals, which is required for the separated axon to degenerate after injury. Conversely, attenuated axon death signaling results in severed axons and their synapses which remain morphologically and functionally preserved for weeks to months.
We use Drosophila and its powerful genetics to study axon death signaling. A recently established novel approach in the wing will be presented that allows for the observation and manipulation with the resolution of single, individual axons of sensory neurons. It led to the discovery and characterization of axundead (axed), which is a novel, essential axon death gene. We’ll share our most recent unpublished insights related to axon death signaling, with a particular focus on Axed.
Axon death signaling is not only activated following injury, it is also engaged in a broad range of neurodegenerative conditions. Defining the molecular machinery that executes axon death could therefore provide exciting targets for therapeutic intervention both in neural injury and in neurodegenerative disease.