ArticlePLoS biology2026
A high-resolution phenotypic screen identifies regulators of CNS axon diameter in zebrafish.
Article in PLoS biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The molecular mechanisms underpinning neuronal morphogenesis remain to be fully understood. A powerful step in uncovering the molecular basis of biological processes is the execution of discovery screens in model systems. Here, we employed zebrafish to identify molecules that regulate axon diameter in the central nervous system. Axon diameter can vary by >100-fold, with larger axons exhibiting faster conduction velocity. Axon diameter influences myelination, can be dynamically regulated, and is altered in disease. However, gaining insights into axon diameter has been challenging due to the small size and complexity of axons in vivo. Therefore, we developed an automated high-resolution live imaging and analysis screening platform to identify pharmacological modulators of the diameter of the large Mauthner axon in zebrafish. We screened 880 compounds and identified 33 hits. Validating this pipeline, we confirmed that compounds affecting beta-2 adrenoceptor and dopamine signaling increase axon diameter. This represents the first subcellular in vivo imaging-based screen to detect changes in axon diameter, providing entry points to study the biology of this key feature of neuronal morphology.
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