Schwann cells and oligodendrocytes read distinct signals in establishing myelin sheath thickness

Schwann cells and oligodendrocytes produce myelin sheaths of widely varying sizes. How these cells determine the size of myelin sheath for a particular axon is incompletely understood. Axonal diameter has long been suspected to be a signal in this process. We have analyzed myelin sheath thickness in L5 lumbar root and spinal cord white matter of a series of mouse mutants with diminished axonal calibers resulting from a deficiency of neurofilaments (NFs). In the PNS, average axonal diameters were reduced by 20-37% in the NF mutants. Remarkably, the average myelin sheath thickness remained unchanged from control values, and regression analysis showed sheaths abnormally thick for a given size of axon. These data show that a genetically induced reduction in axonal caliber does not cause a reduction in myelin sheath thickness in PNS and indicate that Schwann cells read some intrinsic signal on axons that can be uncoupled from axonal diameter. Interestingly, myelin sheaths in the spinal cord of these animals were not abnormally thick, arguing that axonal diameter may contribute directly to the regulation of myelination in the CNS and that oligodendrocytes and Schwann cells use different cues to set myelin sheath thickness.