Cody Call
Cell biology of myelin formation in the central nervous system
Research Interests:
Every thought, sensation, and movement depends on electrical signals traveling along axons, the long cables that connect neurons to one another. In the brain and spinal cord, many axons are wrapped in myelin, an insulating membrane made by glial cells called oligodendrocytes, which allows signals to travel up to a hundred times faster. Beyond speeding things up, myelin controls when each signal arrives at its destination, helping neurons across the brain fire in precise, coordinated patterns. Much of how the brain learns and adapts depends on this coordination, and disrupting it underlies the symptoms experienced in diseases such as multiple sclerosis.
The Call Lab uses a combination of zebrafish and mouse experimental models to define the cellular mechanisms responsible for oligodendrocyte formation and myelination, with an emphasis on live imaging approaches to see how these cells form and behave in the living nervous system. We seek to answer the following questions:
How do oligodendrocytes get made? Close to birth, our central nervous systems are filled with a rapidly proliferating population of oligodendrocyte progenitor cells (OPCs). These cells are retained throughout life, and respond to local cues to differentiate and transform into oligodendrocytes. This transformation is dramatic. An OPC must stop dividing, overhaul which genes are switched on and off, reorganize its cytoskeleton and organelles, and expand its membrane area by nearly 10,000-fold, all in a matter of days. Understanding this process also matters for repair. In multiple sclerosis, OPCs are often present in demyelinated lesions but fail to become new oligodendrocytes. We are asking which signals from the surrounding environment trigger differentiation, and which molecular pathways inside the cell orchestrate these changes so the transformation succeeds.
Once an oligodendrocyte is formed, how does it ensure myelin is put in the right place with the right dimensions? The myelin sheath is a marvel of cell-to-cell interaction. To make one, an oligodendrocyte process must first find and adhere to an axon. The ensheathing process then expands along the axon in two directions, extending along the length of the axon while spiraling around it, adding layer upon layer of membrane. Throughout this process, the oligodendrocyte must ignore other structures with axon-like shapes, such as dendrites and capillaries, and tailor both the number of wraps and the length of each sheath on an axon-by-axon basis. We want to know what signaling takes place at the growing sheath to control these behaviors, how the cell's internal machinery carries them out, and how these decisions are revisited when myelin is remodeled or repaired later in life.
Biography:
- Assistant Professor, University of Notre Dame Biological Sciences
- Postdoctoral Fellow, Oregon Health & Science University (2021-2027)
Education:
- Ph.D., Neuroscience, Johns Hopkins University (2015-2021)
- B.S., Psychology & Biology, Florida State University (2011-2015)
Recent Papers:
- Call CL*, Neely SA, Early JJ, James OG, Zoupi L, Williams AC, Xu YKT, Chandran S, Lyons DA, Monk KR, Bergles DE*. Flexible ensheathment of axons enables myelination of complex CNS networks. Nature 654, 724–733 (2026). https://doi.org/10.1038/s41586-026-10312-1 *co-corresponding
- Call CL, Bergles DE. Cortical neurons exhibit diverse myelination patterns that scale between mouse brain regions and regenerate after demyelination. Nature Communications 12, 4767 (2021). https://doi.org/10.1038/s41467-021-25035-2
- Xu YKT, Call CL, Sulam J, Bergles DE. Automated in vivo tracking of cortical oligodendrocytes. Frontiers in Cellular Neuroscience 15, 667595 (2021). https://doi.org/10.3389/fncel.2021.667595
- Orthmann-Murphy J*, Call CL*, Molina-Castro GC, Hsieh YC, Rasband MN, Calabresi PA, Bergles DE. Remyelination alters the pattern of myelin in the cerebral cortex. eLife 9, e56621 (2020). https://doi.org/10.7554/eLife.56621 *contributed equally
Research Specialties:
- Oligodendrocytes and myelination
- Remyelination and multiple sclerosis
- Cell biology and molecular biology
- Zebrafish and mouse genetics
- In vivo imaging