Unzipped mediates axon guidance of Drosophila melanogaster mushroom bodies through neuron-neuron and neuron-glia interactions

Drosophila mushroom body (MB) neuropil is the regulatory center for learning, memory, and many different behaviors. Besides its functional role, MB is a great model to investigate axon guidance dynamics. The MB consists of three different types of neurons that have very similar yet distinctive axon projection patterns. The morphology and the cellular mechanisms of MB development are well characterized and many genetic tools have been developed that allow researchers to address different questions. The requirement for neuron-neuron interactions during MB axon guidance has been relatively well characterized (Siegenthaler et al., 2015), however the role of neuron-glia interactions during this process are still unresolved. Here, we focused on the role of unzipped (uzip) in MB axon guidance. Initial experiments with mutant lines revealed that uzip is required for proper MB axon guidance. Knockdown experiments in different neuron populatins revealed that expression of Uzip by MB neuron subtypes is required for the interactions between those cells to mediate axon guidance. Apart from neuronal Uzip, glia-specific loss-of-function (LOF) and molecular rescue experiments revealed that Uzip expression glial cells is also required for proper MB development. Taken together, functional analyses experiments revealed that during MB axon guidance Uzip is not only involved in previously defined neuron-neuron interactions but also mediating previously unknown neuron-glia interactions. Additionally, Uzip signaling that navigates MB axons include axon guidance molecules nrg, sema-1a, CadN and drl. All of those molecules were previously shown to be regulating MB axon guidance and this study contributes by both revealing the molecular networks in more detail and also bringing glia into the game.