ZeDiAx: Using zebrafish to discover how axons grow in diameter

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Axon diameter varies up to 100-fold between distinct neurons in the central nervous system. This diversity is relevant for circuit function because there is a positive correlation between increased axon diameters and faster nerve conduction velocity. Indeed, the dynamic regulation of axon diameter might help fine-tune the timing of signal propagation and thus neural circuit function. In addition, axons of distinct sizes are observed altered in neurodevelopmental through to neurodegenerative disorders. Therefore, if we want to fully understand how nervous systems are built, functionally mature, and remain healthy, we need to understand what regulates axon diameter growth. At present, we know surprisingly little about how axons grow to such different diameters in the living nervous system. Through this project, I will unravel the molecular mechanisms underlying axon diameter growth by utilizing the diverse opportunities of zebrafish as a model system. By first undertaking a chemical-based screen approach and visualizing changes in axon diameters I will identify novel molecular signals that impact diameter growth. I will then employ cutting-edge live imaging techniques to further investigate precisely how these molecules influence diameter growth over time. Through behavioural assays and functional imaging techniques, I will also investigate how changes in axon diameter impact action potential conduction and circuit function. The outcomes of this multidisciplinary approach will provide new insights into our understanding of axon diameter growth and regulation that I ultimately aim to translate to mammals and humans. This project will contribute to the research output and visibility of Europe and will foster the launch of my future research career.