Which signals regulate myelination?

How might neural activity affect myelination?

How dO conduction properties mature along axons over time? 

How does demyelination occur and how does it affect neurons? 

How can we find new treatments for demyelinating diseases?

Many signals regulate myelination and myelinated axon formation, health and function. For example, we have found that oligodendrocyte neurofascin regulates both myelin sheath targeting and growth (Klingseisen et al., 2019), and NKCC1 the integrity of mature myelin (Kegel et al., 2020), that myelin calcium signalling regulates sheath formation, growth and retraction (Baraban et al., 2018), and that endothelin signalling (Swire et al., 2019) and mGluR5 mediate activity-dependent myelination (Braaker et al., 2025).

We know that axons make synaptic connections with oligodendrocytes, essentially communicating with them as if they were other neurons. Research in our lab showed that oligodendrocytes adjust their patterns of myelination depending on the activity of axons in their vicinity (see Mensch et al., 2015; Koudelka et al., 2016; Almeida et al., 2018), and that vesicle fusion is concentrated in hotspots at the growing edge of a sheath, and that myelination itself promotes the signal, a feedforward loop that consolidates myelin on selected axons (Almeida et al., 2021).

Numerous factors can influence the conduction of action potentials. Axon diameter, myelination and axonal domain organisation all exert major and inter-dependent effects on conduction. However, how these features mature over time and how they collaborate or are independently regulated to influence conduction along single axons in neural circuits in vivo is not known. We combine highly detailed live imaging of myelinated axons with manipulations of key parameters to assess how form relates to function (Madden et al., 2021;, Bin et al., 2024)

Myelin is a key player in nervous system function. As such, it is crucial to understand how myelin develops and interacts with other cells in the brain. However, the overarching goal of our research is to improve the prognosis of debilitating neurodegenerative diseases. Multiple sclerosis (MS) is a major demyelinating disorder of the brain, in which our immune system aberrantly attacks myelin. Due to the loss of myelin, neuronal function is impaired, and the neurons often degenerate. Currently, we are unable to prevent neurodegeneration in MS, but we know that remyelination can occur.

To study how the nervous system is affected after demyelination, and in the hope of finding new treatments, we created a zebrafish model of demyelination. Sarah Neely is studying the oligodendrocytes which survive demyelination, and how well they fare (Neely et al., 2020). Donia Arafa also want to understand how this model affects neuronal function, since we still don’t know what causes the neurons to degenerate following demyelination.

Using the demyelination model, Katy Marshall-Phelps and Marcus Keatinge are undertaking an automated screen to test a library of drugs with the potential to boost remyelination. Such projects are possible thanks to the work of Jason Early, our resident microscope whisperer (Early et al., 2018).