Forces driving myelin wrapping In oligodendrocytes

In the brain’s central nervous system a protective layer, called myelin, ensheaths nerve cells and insulates neuronal action potentials. Loss of this protective myelin membrane results in severe patient disabilities. In order to function, the myelin must wrap around the axon multiple times. The mechanism that powers myelin wrapping is unknown. Most cells change shape to grow and move by building a “scaffold” from a protein called actin, a part of the cell’s skeleton. Importantly, recent work from my postdoc mentor, Brad Zuchero, has utilized established primary culture and in vivo systems to study myelin extension and discovered that the actin in OLs must completely disassemble prior to wrapping. Given that forces generated by actin do not exist during myelin wrapping, I propose that forces generated from other cellular processes power wrapping. One source could be from compaction of the myelin membrane. During myelination the cell compacts its membrane while it wraps an axon. I believe that this could push the membrane forward much like squeezing a balloon. The other process could be from adhesion around the expanding membrane. During myelination, the part of membrane that is growing is in contact with itself and the axon. I believe the membrane could be attaching to itself or the axon to pull the membrane forward like tape. Utilizing neuroscience and bioengineering techniques from the Stanford labs of Brad Zuchero and Alex Dunn I have created a unique toolbox that will allow me to thoroughly study our hypotheses of actin-independent myelin membrane expansion in the brain. Identifying the mechanism of myelin wrapping is important in understanding neural development and is a critical first step towards creating much needed therapeutic approaches to stimulate remyelination in patients with demyelinating diseases.

Project Details

Funding Type:

Interdisciplinary Scholar Award

Award Year:


Lead Researcher(s):

Team Members:

J Bradley Zuchero (Sponsor, Neurosurgery)
Alexander Dunn (Sponsor, Chemical Engineering)