Axonal regulation of myelin protein mRNA levels in actively myelinating Schwann cells

Abstract

Upon transection of a peripheral nerve, axons distal to the transection degenerate. As a consequence of this axonal degeneration, myelin- forming Schwann cells cease biosynthesis of new myelin membrane, contribute to phagocytosis of previously formed myelin, and markedly down-regulate expression of myelin-specific markers. Among the most prominent of these down-regulated markers are the major structural proteins of peripheral myelin, Po and myelin basic protein (MBP). We have used slot blot and in situ hybridization techniques to demonstrate that for actively myelinating Schwann cells, down-regulation of the Po and MBP genes occurs primarily at the level of mRNA expression. Together with other recent data, these findings strongly argue for axonal modulation of Po and MBP gene transcription during active myelination.

Interactions of Sox10 and Egr2 in myelin gene regulation

“…Since the identification of the gene encoding Mpz (Lemke and Axel, 1985), several studies have probed its transcriptional regulation. The large increase of Mpz expression in myelinating Schwann cells depends on axonal signals (Lemke and Chao, 1988) and declines dramatically after nerve injury (Trapp et al, 1988). Moreover, the MPZ gene is commonly mutated in human peripheral neuropathies such as Charcot-Marie-Tooth disease (reviewed in Wrabetz et al, 2004;reviewed in Shy, 2005).…”

A myelin protein is encoded by the homologue of a growth arrest-specific gene.

“…Several proteins are known to be upregulated or reexpressed by Schwann cells after sciatic lesions, including nerve growth factor (7), the nerve growth factor receptor (8), and some neuronal cell adhesion molecules like Li and N-CAM (9, 10). In contrast, myelin genes are strongly repressed soon after injury (4,11).…”

“…During development, Schwann cells cease proliferation concomitant to the initiation of myelin synthesis (3). This process is reversed in Wallerian degeneration when the Schwann cells downregulate myelin gene expression and resume proliferation (4,5). If the injured peripheral nerve is allowed to regenerate, the Schwann cells will recapitulate the developmental program leading to functional recovery (6).…”

Activation of Myelin Genes during Transdifferentiation from Melanoma to Glial Cell Phenotype

“…Similarly, fibroblast growth factor or transforming growth factor-␤ inhibit Po gene expression (24). Axonal contacts are thought to provide positive stimuli for myelin gene expression in SC cultures (25) and in transected nerves (26). The molecules mediating these axonal cues are not well known.…”