Regulation of oligodendrocyte structure during brain development.

What is it about?

Oligodendrocytes are specialized cells in our brain that provide a coating of the axons, the long “cable” like parts of neurons. This coating, termed myelin, helps speed the electrical signals traveling along axons and support neuronal function in various ways. To generate myelin, oligodendrocytes extend their membrane and wrap it multiple times around the axon. This extensive structural formation is powered by a cellular machinery of fibers termed the actin cytoskeleton. Our previous work revealed that the oligodendrocyte actin cytoskeleton is highly dynamic during brain development, yet how the oligodendrocyte cytoskeleton is regulated during myelination remains poorly understood. Here, we identify the transcription factor SRF (serum response factor) as essential for myelination. SRF directly regulates expression of actin regulatory genes in oligodendrocytes and, surprisingly, also inhibits disease-associated gene expression.

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Photo by Adrien Converse on Unsplash

Photo by Adrien Converse on Unsplash

Why is it important?

We recently discovered that oligodendrocytes in the aged mouse brain express lower levels of SRF and speculated that it could be a reason for their impaired ability to form myelin with aging. Excitingly, we found that re-exposure of the brain to young cerebrospinal fluid could elevate SRF levels in oligodendrocytes, promote their growth and improve memory in aged mice. Our findings in the current paper uncover more mechanistic detail on the role of SRF in myelin formation that may represent a therapeutic target for restoring myelin in the aged or diseased brain.