ZeDiAx: Using zebrafish to discover how axons grow in diameter
Lead Research Organisation:
University of Edinburgh
Department Name: Centre for Discovery Brain Sciences
Abstract
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.
Organisations
Publications

Bin JM
(2025)
Developmental axon diameter growth of central nervous system axons does not depend on ensheathment or myelination by oligodendrocytes.
in bioRxiv : the preprint server for biology
Description | Through the work of this award, a large-scale study was carried out to identify the signals and receptors that determine how our nerve cables grow to the correct diameter. This is important because the diameter of our nerve cables determines how quickly electrical impulses are conducted along those cables. As part of this award, we carried out a screen of >800 drugs to identify those that influence nerve cable (axon) diameter in young zebrafish, in which we can see single axons at very high resolution. We found a range of drugs that either increase or decrease axon diameter. Because these drugs are known to to act as specific molecular signals or to activate or inhibit known receptors, we can tell which signals and receptors in the living animal. This provides new insights into how our brain is built and functions, and how it can be altered in disease. |
Exploitation Route | The outputs of this project have already and will continue to lay the foundations for development of a new research field. This will be driven in part by the postdoctoral fellow supported through this award, and by our wider team, through further funding, and in due course, by the wider research community. |
Sectors | Healthcare Pharmaceuticals and Medical Biotechnology |