Cellular and molecular mechanisms of myelinated axon formation and regeneration in vivo.

• Applicant: Dr. Tim Czopka, Ph.D.
• Subject Area: Developmental Neurobiology
• Term: from 2014 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 252784993

The majority neuronal projections (axons) in our brain are eventually ensheathed by a structure called myelin, which is formed by specialized cells called oligodendrocytes as they iteratively wrap their cell membranes around the axon. This ensheathment supports axon function by restricting nerve impulse propagation to short unmyelinated gaps between individual myelin sheaths (the nodes of Ranvier), and by the local provision of metabolites to the axon. The myelination of axons is not as stereotyped as it was long believed and it may adaptively change in response to experience and neuronal activity – with implications for interneuronal communication and learning. Damage to myelin, as it can occur in diseases and injuries, impairs axon function and ultimately leads to its degeneration when damaged myelin is not repaired in a regenerative process called remyelination. The mechanisms that orchestrate how an axon gets myelinated and repaired along its length in the healthy and diseased central nervous system are not well understood.This proposal aims to investigate how axonal components of the node of Ranvier can determine the patterning of myelination along an axon during development and in response of experimental myelin damage. For this, my group uses zebrafish as model organism due to its suitability for high-resolution live cell imaging and genetic manipulation. In our previous work, we have generated reagents to label individual axons, surrounding myelin and nodes of Ranvier to carry out long-term longitudinal studies of axon myelin patterns over time. We have developed assays of experimental demyelination using targeted ablation of oligodendrocytes. Our work revealed the existence of a homeostatic control of axon myelin patterns by the controlled maintenance and remodeling myelin sheath length. We will now test how such tight control of myelin length can be governed by the axon itself, specifically by components of the node of Ranvier. The results obtained from our work will provide insights into control of formation and repair of axon myelination patterns by cell-intrinsic and -extrinsic parameters.

• DFG Programme: Independent Junior Research Groups