In the 2008 Annual Review of Neuroscience, Nave and Trapp review the recent research in the signalling mechanisms responsible for the myelination of axons in the white matter of the CNS.
It is well established that axon signals, not Schwann cells themselves, are responsible for the myelination of cells. This was shown because given Schwann cells can be exposed to certain axons and not produce myelin, but when confronted with regenerating axons from a the myelinated axon of a tissue graft these same Schwann cells will produce myelin.
These axon signals appear to be linked to the size of the axon. Not only is there a direct relationship between size of the axon and the likelihood of myelination, but when unmyelinated postganglionic nerves of the salivary gland are surgically enlarged to twice their original size, they have an increased ability to recruit Schwann cells for myelination.
The neuregulin NRG-1 is believed to be the most important mitogen and recruiter of unmyelinated Schwann cells. The amount of NRG-1 regulates the thickness of the myelin sheath, and mutant organisms with less NRG-1 production have thinner sheathing than wildtypes.
Recent research shows that oligodendrocytes also play an important and distinct role in supporting the axons and protecting the neurons they are associated with. The authors also discuss the evidence that glial support for axons developed in the evolutionary lineage before glial cells began to myelinate axons.
These findings present some news ways of approaching mice models of demylination such as proteolipid protein knockout mice, whose axons are not actually demylinated, but still lose structural support and have early deaths starting at ~ 12 months. Down the road, they will hopefully be able to be applied to human patients as well.
Nave KA, Trapp BD. 2008 Axon-glial signaling and the glial support of axon function. Annual Review of Neuroscience 31: 535-561. doi:10.1146/annurev.neuro.30.051606.094309.