Restricted growth of Schwann cells lacking Cajal bands slows conduction in myelinated nerves

Abstract

Nerve impulses are propagated at nodes of Ranvier in the myelinated nerves of vertebrates. Internodal distances have been proposed to affect the velocity of nerve impulse conduction; however, direct evidence is lacking, and the cellular mechanisms that might regulate the length of the myelinated segments are unknown. Ramón y Cajal described longitudinal and transverse bands of cytoplasm or trabeculae in internodal Schwann cells and suggested that they had a nutritive function. Here we show that internodal growth in wild-type nerves is precisely matched to nerve extension, but disruption of the cytoplasmic bands in Periaxin-null mice impairs Schwann cell elongation during nerve growth. By contrast, myelination proceeds normally. The capacity of wild-type and mutant Schwann cells to elongate is cell-autonomous, indicating that passive stretching can account for the lengthening of the internode during limb growth. As predicted on theoretical grounds, decreased internodal distances strikingly decrease conduction velocities and so affect motor function. We propose that microtubule-based transport in the longitudinal bands of Cajal permits internodal Schwann cells to lengthen in response to axonal growth, thus ensuring rapid nerve impulse transmission.

Neuregulin/ErbB Signaling in Developmental Myelin Formation and Nerve Repair

“…Myelin electrically insulates axons and allows fast propagation of nerve impulses by saltatory conduction. The overall conduction velocity of the myelinated axon is determined by myelin and axonal thickness, internodal length and myelin integrity (Waxman, 1980;Court et al, 2004). The overall organization of the myelin sheath is similar in the PNS and CNS, but substantial differences exist in development, assembly and molecular composition of the myelin, or in the extrinsic signals and transcription factors that drive myelination (Quarles et al, 2006;Brinkmann et al, 2008;Emery, 2013;Hornig et al, 2013).…”

Biology and pathology of nonmyelinating Schwann cells

“…B is modified from Ebenezer et al (2007). velocity is linearly related to the total diameter of the fiber (axonal diameter plus twice the myelin sheath thickness) (Smith and Koles, 1970;Waxman, 1980). There is also an influence from internodal distance (Court et al, 2004). It is well recognized that the nodes, each 1 lm in length, represent the electrogenic zones into which sodium channels are collected.…”

Regulation of Schwann cell function by the extracellular matrix

“…L-periaxin is required for the formation of the DG-dystrophin-related protein-2 (DG-DRP2) complex and is involved in the link between the ECM and the Schwann cell cytoskeleton (Sherman et al, 2001). Schwann cells lacking L-periaxin exhibit disruption of the Cajal bands, a cellular structure with a nutritive function, resulting in reduced Schwann cell length during nerve growth (Court et al, 2004). It is known that dystrophic mice also have reduced internodal length (Jaros and Jenkison, 1983).…”