Rewriting the evolutionary history of the neuron

Almost all features of our neurons, from the ion channels that underlie electrical signaling to cellular structures such as axons, dendrites and synapses are ancient and are therefore shared among all living bilaterian animals. However, one critical feature that appeared to have a much more recent evolutionary origin was the axon initial segment (AIS), a specialized compartment at the beginning of the axon that serves as a barrier for maintaining axon identity and as the site of action potential initiation. The AIS was believed to be a recent vertebrate innovation for precision signaling, because the giant ankyrins which link AIS ion channels to the cytoskeleton and are required for barrier formation were believed to be vertebrate-specific. We collaborated with the Rolls lab to show that giant ankyrins instead have a much earlier origin in an ancestor of all bilaterians. They appear to organize an AIS-like domain in the axons of fly sensory neurons, suggesting that the AIS itself is part of that ancient, shared bilaterian neuronal heritage. We think this work will establish Drosophila as a model system for detailed molecular genetic dissection of AIS function. This is important because AIS biology has many important open questions and AIS dysfunction plays a role in a variety of nervous system disorders.