What regulates axonal diameters in the central nervous system?

• Applicant: Dr. Maria Eichel-Vogel
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2021 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 493410640

Axon diameter, the cross-sectional size of the axon, varies up to 100-fold between distinct neuronal subtypes in the central nervous system (CNS) and its increase correlates positively with faster nerve conduction velocity. However, in contrast to many aspects of neuronal and axonal development we know comparatively little about axon diameter growth. It appears plausible that axon size not only provides different conduction opportunities, but that its dynamic regulation might fine-tune circuit function. Furthermore, axons of distinct sizes have different susceptibilities to diseases. Therefore, it is crucial to understand what regulates axonal diameters in the CNS. To study the mechanisms underlying axon diameter growth I will use zebrafish as a model system. I hypothesize that the developmental program of individual neurons, and their interactions with postsynaptic targets establish differences in axonal diameters. To test this, I will image individual neurons with differently sized axons over time and manipulate their interactions with postsynaptic targets. To unveil molecular mechanisms regulating axon diameters in the CNS, I will take an unbiased screening approach using high-resolution transcriptome sequencing and candidate gene targeting. In addition, I test the prediction that axon diameters are either maintained or dynamically refined by neural and synaptic activity. To do so, I will visualize and manipulate neuronal and synaptic activity, and monitor axonal diameters in vivo. Together, this work will provide cellular and molecular insights into a fundamental feature of neurons that impacts nervous system formation, function and healthy maintenance.

• DFG Programme: WBP Fellowship
• International Connection: United Kingdom
• Host: Professor Dr. David Lyons