The Stages of Myelination
A Summary of the Series of Events in Myelin Ensheathment of Axons
Sep 20, 2009
The effects of myelination are significant. Myelinated axons can propagate neural signals faster than unmyelinated ones, having the most significant time difference in the axons with larger diameters. Many scientists have claimed this is one big step in human evolution – the ability to think faster than other creatures.
Myelinated axons also allow axons to stay more robust, even across distances on the scale of millimeters, which is a very long distance if you're thinking of the diameter of a microscopic axon.
While people don't yet know all the mechanisms that make an oligodendrocyte choose which axon to myelinate, whether the axon in question has to have a certain activity pattern or be a certain size, but the four stages of myelination have been ascertained as will be described below.
Stage 1, Axon Contact
Axons express proteins. These proteins are transported in vesicles and run up and down molecular tracks of microtubules with little molecular motors called kinesins and dyneins. Usually, axons produce two proteins (among others) called NCAM and L1. Upon contact with a glial cell, the axon ceases to produce NCAM and reduces its production of L1.
Cellular adhesion molecules like N-cadherin might also be important for this initial contact. One might imagine these cell adhesion molecules stabilize the connection between the glial neurite (the arm of the glial cell) and the axon.
Stage 2, Glial Cell Gene Production
Glial cells change their gene production upon coming into contact with axons. The premyelinating genes best understood include GalC, PLP/DM20, CNP, MAG, and MBP. Many genes whose functions aren't yet fully known are also associated with gene production. Some of these include Nogo-A and MOSP. Nogo-A is a molecule involved in many aspects of axon development, including axon guidance. How does an axon know where to go? Its function in myelination is less well understood.
Neuregulin-1 and the Jagged/Notch combination serve as positive and negative cell differentiation regulators, respectively.
Stage 3, Axon Ensheathment
At this stage, the glial cell sends out premyelinating processes to spirally wrap around the axon. MBP and PLP are two possible candidates for the cellular adhesion process of this spiral wrap.
Any oligodendrocytic processes that have not come into contact with axons at this stage are lost.
Stage 4, Maturation
After sending out these initial spirally wrapping processes, the glial cells begin to fully encase the axon in myelin, forming a coiled sheath around a segment of the axon. This sheath develops inwardly, wrapping underneath its own previous layers.
Unanswered Questions
Following is a short list of some of the unanswered questions regarding oligodendrocytes and myelination:
- One oligodendrocyte seems to myelinate axons of similar size. How can an oligodendrocyte judge the size of an axon?
- How does an oligodendrocyte respond to axonal activity?
- How are non-contacted oligodendrocytic processes lost?
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