Control of myelin formation by axon caliber. (With a model of the control mechanism)

Abstract

The relation between the growth of axons and the development of their myelin sheaths was determined in rats for normal, myelinating sciatic nerves, and for an experimental model allowing to retard or accelerate axon growth. Axon caliber was measured, and sheath development was determined from measurements of thickness (light microscopy), from counts of the number of turns of myelin lamellae (electron micrographs), and from the rate of the incorporation of acetate‐H 3 into ether‐ethanol extractable lipids. An excellent correlation between changes in sheath thickness and acetate‐H 3 incorporation was obtained for all experiments. For the myelinating nerves the changes in the rate of acetate‐H 3 incorporation were related specifically to the rate with which new length of myelin leaflet was added to the existing turns of sheath. The rate of axonal growth was manipulated by applying a snug ligature around the nerve by the fourteenth day, allowing the nerve to compress itself by its own growth. Most axons passed the constriction without interruption, but they were markedly hypoplastic distal to the constriction. After removal of the ligature these axons regrew to their normal caliber ranges. Examination of myelin sheath development in this model showed that retardation of axon growth retarded sheath growth, while acceleration of axon growth accelerated sheath growth. Thus, the rate of axon growth appeared to be the factor controlling the rate of myelin formation by the sheath cells. An appendix describes a model consisting of two interrelated feedback mechanisms by which expansion of the axon may directly control the number of turns of myelin lamellae formed by the sheath cell. The model correspons on all points to established features in the fine structure of fibers.