Structure and Function of Myelin Protein Genes

Mikoshiba, Katsuhiko; Okano, Hideyuki; Tamura, Toshiaki; Ikenaka, Kazuhiro

doi:10.1146/annurev.ne.14.030191.001221

Cited by 75 publications

(43 citation statements)

References 78 publications

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“…The latter have a partial deletion in the gene encoding myelin basic protein (MBP) [22][23][24][25]. The present data establish the importance of graft-derived oligodendrocytes in the functional recovery of the injured spinal cord after NS/PC transplantation.…”

Section: Introductionsupporting

confidence: 59%

Significance of Remyelination by Neural Stem/Progenitor Cells Transplanted into the Injured Spinal Cord

et al. 2011

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Previous reports of functional recovery from spinal cord injury (SCI) in rodents and monkeys after the delayed transplantation of neural stem/progenitor cells (NS/PCs) have raised hopes that stem cell therapy could be used to treat SCI in humans. More research is needed, however, to understand the mechanism of functional recovery. Oligodendrocytes derived from grafted NS/PCs remyelinate spared axons in the injured spinal cord. Here, we studied the extent of this remyelination's contribution to functional recovery following contusive SCI in mice. To isolate the effect of remyelination from other possible regenerative benefits of the grafted cells, NS/PCs obtained from myelin-deficient shiverer mutant mice (shi-NS/PCs) were used in this work alongside wild-type NS/PCs (wt-NS/PCs). shi-NS/PCs behaved like wt-NS/PCs in vitro and in vivo, with the exception of their myelinating potential. shi-NS/ PC-derived oligodendrocytes did not express myelin basic protein in vitro and formed much thinner myelin sheaths in vivo compared with wt-NS/PC-derived oligodendrocytes. The transplantation of shi-NS/PCs promoted some locomotor and electrophysiological functional recovery but significantly less than that afforded by wt-NS/PCs. These findings establish the biological importance of remyelination by graft-derived cells for functional recovery after the transplantation of NS/PCs into the injured spinal cord.

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Section: Introductionsupporting

confidence: 59%

Significance of Remyelination by Neural Stem/Progenitor Cells Transplanted into the Injured Spinal Cord

et al. 2011

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“…Therefore, aberrant proprioceptive axons appear to alter the localization of myelinating oligodendrocytes in the dorsal spinal cord in Plxna1 mutants (Yoshida et al, 2006). To determine the temporal and spatial patterns of oligodendrocyte differentiation in the dorsal spinal cords of Sema6d heterozygous and homozygous mutant mice, we monitored the expression of two oligodendrocyte markers: myelin associated glycoprotein (Mag) and myelin basic protein (Mbp) (Mikoshiba et al, 1991) at P0 and P10 by in situ hybridization. At P0, there were a few Mag-and Mbp-positive oligodendrocytes in the spinal cords of Sema6d heterozygous and homozygous mutants (see Fig.…”

Section: Ectopic Localization Of Myelinating Oligodendrocytes In the mentioning

confidence: 99%

Ectopic myelinating oligodendrocytes in the dorsal spinal cord as a consequence of altered semaphorin 6D signaling inhibit synapse formation

et al. 2011

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SUMMARYDifferent types of sensory neurons in the dorsal root ganglia project axons to the spinal cord to convey peripheral information to the central nervous system. Whereas most proprioceptive axons enter the spinal cord medially, cutaneous axons typically do so laterally. Because heavily myelinated proprioceptive axons project to the ventral spinal cord, proprioceptive axons and their associated oligodendrocytes avoid the superficial dorsal horn. However, it remains unclear whether their exclusion from the superficial dorsal horn is an important aspect of neural circuitry. Here we show that a mouse null mutation of Sema6d results in ectopic placement of the shafts of proprioceptive axons and their associated oligodendrocytes in the superficial dorsal horn, disrupting its synaptic organization. Anatomical and electrophysiological analyses show that proper axon positioning does not seem to be required for sensory afferent connectivity with motor neurons. Furthermore, ablation of oligodendrocytes from Sema6d mutants reveals that ectopic oligodendrocytes, but not proprioceptive axons, inhibit synapse formation in Sema6d mutants. Our findings provide new insights into the relationship between oligodendrocytes and synapse formation in vivo, which might be an important element in controlling the development of neural wiring in the central nervous system.

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“…MBP is a primary structural component of the myelin sheath (Mikoshiba et al 1991). This protein is highly positively charged and functions in the compaction of membrane layers in developing myelin.…”

Section: Identification Of Qk1 Binding Sites In Mbp Mrnamentioning

confidence: 99%

Specificity of the STAR/GSG domain protein Qk1: Implications for the regulation of myelination

Ryder

Williamson²

2004

RNA

110

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Inadequate formation and maintenance of myelin is the basis for several neurodegenerative disorders, including leukodystrophy and multiple sclerosis. In mice, oligodendrocyte differentiation and subsequent formation of myelin requires the Quaking gene. Mutation of this gene leads to embryonic lethality or to a trembling phenotype characteristic of dysmyelination. Quaking encodes Qk1, a member of the highly conserved STAR/GSG family of RNA-binding proteins that function as master developmental regulators in higher eukaryotes. Qk1 has been implicated in the regulation of alternative splicing, stability, and translation control of mRNAs that code for myelin structural components in glial cells. We have used quantitative gel mobility shift and fluorescence polarization assays to define the nucleotide sequence specificity of the Qk1 STAR/GSG domain, and to probe the interaction between Qk1 and the 3-untranslated region (UTR) of myelin basic protein (MBP) mRNA. The results show that Qk1 recognizes a hexanucleotide consensus element that is similar although not identical to the specificity determinant recognized by the Caenorhabditis elegans STAR/GSG protein GLD-1. Several consensus sites are present in the 3-UTR of MBP mRNA. The highest affinity site is located within the RNA localization region, suggesting a possible role for Qk1 in restricting MBP mRNA to the myelin compartment.

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Structure and Function of Myelin Protein Genes

Cited by 75 publications

References 78 publications

Significance of Remyelination by Neural Stem/Progenitor Cells Transplanted into the Injured Spinal Cord

Significance of Remyelination by Neural Stem/Progenitor Cells Transplanted into the Injured Spinal Cord

Ectopic myelinating oligodendrocytes in the dorsal spinal cord as a consequence of altered semaphorin 6D signaling inhibit synapse formation

Specificity of the STAR/GSG domain protein Qk1: Implications for the regulation of myelination

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