Studies of the Initiation of Myelination by Schwann Cells

Abstract

The rapid morphologic changes in Schwann cells and in their relationships to axons during the transition from the premyelinating to the myelinating state have been known for more than 15 years. The sorting of axons by dividing Schwann cells, the establishment of a 1:1 relationship between a postmitotic Schwann cell, and the onset of myelin sheath formation have all been described in detail. However, the chain of molecular events and mechanisms by which these morphologic changes are regulated has not been elucidated. In this chapter we have reviewed results that strongly suggest that the adhesion molecule L1 is one of the important determinants that mediate the elongation of the Schwann cell along the axon, and the extension of Schwann processes to engulf axons. Thus, L1 functions to promote the spreading of the Schwann cell process over the surface of the axon. L1 does not appear to be exclusively involved in the adhesion of Schwann cells to axons, in the activation of Schwann cell proliferation by axons, or in the induction of synthesis of extracellular matrix proteins. The results from the anti-L1 blocking experiments further provided clues for an understanding of how the expression of GalC and MAG, which are both likely to be involved in the initiation of myelination, are regulated. These results imply that the overall regulation of expression of these early myelin components could require controls other than a single signaling mechanism derived from contact with axons. We propose that the deposition of basal lamina or one of its components could also be involved. Finally, the results from anti-GalC-blocking experiments indicated that GalC is involved in the mechanism of early growth of the myelin spiral.

Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling

“…To further assess the role of Sirt2 signaling for SC myelination, we used dorsal root ganglion (DRG)/SC cocultures, a valuable model for studying axon-glia interactions during myelin formation (35,36). Consistent with our in vivo data, Sirt2 knockdown exclusively in SCs by lentivirus-mediated delivery of Sirt2 siRNAs significantly reduced the number of anti-MBP-labeled myelin profiles (Fig.…”

Glial Cell Line-Derived Neurotrophic Factor Alters Axon Schwann Cell Units and Promotes Myelination in Unmyelinated Nerve Fibers

“…Tissue-culture studies have shown that four agents, NGF (Wood et al, 1990;Bahr et al, 1991), progesterone (Koenig et al, 1995), insulin-like growth factor-1 (Russell et al, 1998), and brainderived nerve growth factor (Chan et al, 2001) can sustain or increase the myelination of small axons in vitro. Our in vitro data have shown that GDNF is another agent capable of sustaining the myelination of nerve fibers.…”

“…The factors that determine the myelinated phenotype are not completely understood. Many investigators presume that specific axolemmal molecular signals are involved (Wood et al, 1990), but some data suggest that axonal caliber may be sufficient (Voyvodic, 1989); in general, unmyelinated fibers are smaller and myelinated fibers are larger. This study demonstrates that the administration of high doses of a growth factor to rats can change the phenotype of axons from unmyelinated to myelinated.…”

Neural Cell Adhesion Molecule L1-Transfected Embryonic Stem Cells Promote Functional Recovery after Excitotoxic Lesion of the Mouse Striatum

“…L1 promotes neuronal survival, neurite outgrowth (Lemmon et al, 1989;Appel et al, 1993;Chen et al, 1999;Kleene et al, 2001;Dong et al, 2003), and synaptic plasticity, as shown by modification of synaptic efficacy both in vitro and in vivo as well as in learning and memory as seen in L1-deficient mice and humans (Luthi et al, 1996;Fransen et al, 1998a,b;Tiunova et al, 1998;Wolfer et al, 1998;Demyanenko et al, 1999;Pradel et al, 2000;Law et al, 2003;Saghatelyan et al, 2004;Venero et al, 2004). Furthermore, L1 is involved in myelination in the central and peripheral nervous systems (Seilheimer et al, 1989;Wood et al, 1990;Haney et al, 1999;Barbin et al, 2004). We have shown previously that L1 influences differentiation of neural stem cells into neurons in vitro (Dihné et al, 2003).…”