How does axon-oligodendrocyte adhesion mediate myelin formation and repair in vivo?

• Applicant: Dr. Sophie Siems
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 565898524

Accurate myelination of neuronal circuits is crucial for the efficient function of the vertebrate nervous system, as the exact amount of myelin ensheathing an axon influences the speed and energy efficiency of neuronal transmission. The importance of myelination becomes particularly evident in diseases such as multiple sclerosis (MS), where destruction of myelin disrupts nerve conduction and ultimately leads to long-term neuronal damage. MS is the most common neurodegenerative disease in young adults and often progresses to a chronic, untreatable stage. The chronic phase is attributed to limited remyelination, as regenerated myelin sheaths following myelin damage are typically shorter and thinner than healthy myelin, failing to adequately support axonal function3. Enhancing appropriate remyelination and preventing nerve damage is thus a critical therapeutic need for MS patients. Archiving this requires a deeper understanding of factors regulating accurate myelin growth and efficient repair. Recent studies suggest that the accuracy of myelination can be controlled by regulating adhesion of the myelin membrane to the underlying axon. For instance, experimentally inducing insufficient adhesion disrupts myelin formation, targeting and growth. I thus propose that cellular adhesion is a key mechanism underlying accurate axonal myelination during both development and remyelination. However, how adhesion is regulated along individual axons to ensure correct myelin formation, growth and repair remains unknown. Using zebrafish as a model system, I will combine advanced gene-editing with cutting-edge live-imaging and proteomics tools to investigate the regulation of oligodendroglial adhesion proteins during myelin formation, growth and repair.

• DFG Programme: WBP Fellowship
• International Connection: United Kingdom
• Host: Dr. Rafael Almeida