Molecular Biology and Neurogenetics of Myelin Proteolipid Protein

Nave, Klaus‐Armin; Schneider, Armin; Readhead, Carol; Griffiths, I. R.; Pühlhofer, Anja; Bartholomä, Angelika; Graf, Susanna; Kiefer, Beate

doi:10.1007/978-1-4615-2435-9_12

Cited by 5 publications

(3 citation statements)

References 25 publications

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“…These strains harbor mutations of myelin basic protein (Roach et al, 1983), myelin proteolipid protein (Phillips, 1954), and an unknown protein (Campagnoni, 1988), respectively. These mutations prevent myelin formation on most CNS axons but enable oligodendroglia to mature to varying degrees (Nave, 1994). Together, these studies establish that regional caliber growth, local neurofilament accumulation, and interneurofilament spacing are regulated by extrinsic glial signals and that myelin formation is not required for axons to achieve full-caliber expansion and regional neurofilament accumulation.…”

mentioning

confidence: 75%

Oligodendroglia Regulate the Regional Expansion of Axon Caliber and Local Accumulation of Neurofilaments during Development Independently of Myelin Formation

Sánchez¹,

Hassinger²,

et al. 1996

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Axon caliber may be influenced by intrinsic neuronal factors and extrinsic factors related to myelination. To understand these extrinsic influences, we studied how axon-caliber expansion is related to changes in neurofilament and microtubule organization as axons of retinal ganglion cells interact with oligodendroglia and become myelinated during normal mouse brain development. Caliber expanded and neurofilaments accumulated only along regions of the axon invested with oligodendroglia. Very proximal portions of axons within a region of the optic nerve from which oligodendrocytes are excluded remained unchanged. More distally, these axons rapidly expanded an average of fourfold as soon as they were recruited to become myelinated between postnatal days 9 and 120. Unmyelinated axons remained unchanged. Axons ensheathed by oligodendroglial processes, but not yet myelinated, were intermediate in caliber and neurofilament number. That oligodendrocytes can trigger regional caliber expansion in the absence of myelin was confirmed using three strains of mice with different mutations that prevent myelin formation but allow wrapping of some axons by oligodendroglial processes. Unmyelinated axons persistently wrapped by oligodendrocytes showed full axon caliber expansion, neurofilament accumulation, and appropriately increased lateral spacing between neurofilaments. Thus, signals from oligodendrocytes, independent of myelin formation, are sufficient to induce full axon radial growth primarily by triggering local accumulation and reorganization of the neurofilament network.

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mentioning

confidence: 75%

Oligodendroglia Regulate the Regional Expansion of Axon Caliber and Local Accumulation of Neurofilaments during Development Independently of Myelin Formation

Sánchez¹,

Hassinger²,

et al. 1996

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“…Studies in animal models, particularly in the mouse, contributed immensely to our understanding of PLP and PMP22. The biology of myelin proteolipid protein has been comprehensively reviewed elsewhere (Lemke, 1993;Nave et al, 1994). Mutations in PLP identified in a number of animal models are listed in Table 1.…”

Section: The Plp Gene and Neuropathies Of The Central Nervous Systemmentioning

confidence: 99%

Charcot-Marie-Tooth Disease and Related Inherited Myelin Disorders: Molecular Genetics and Implications for Gene Therapy

Roa¹,

Lupski²

1994

ILAR Journal

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“…Proteolipid protein (PLP) has been traditionally assigned a structural role in the nervous system. However, the remarkable degree of evolutionary conservation of the plp gene amongst mammals (Nave et al, 1994) and the pleiotropic effects of mutations (Duncan, 1990;Griffiths et al, 1995b) suggest that some functions of this gene are not yet known. The plp gene encodes two proteins, PLP and DM-20, which result from the 0 1996 Wiley-Liss, Inc.…”

Section: Introductionmentioning

confidence: 99%

Evidence that some oligodendrocyte progenitors in the developing optic pathway express the plp gene

Fanarraga

Dickinson

Sommer

et al. 1996

Glia

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DM‐20, a product of the proteolipid protein (plp) gene, has been demonstrated in the spinal cord of the mouse embryo as early as embryonic day 12 (E12) in certain cells, some of which are identifiable as oligodendrocyte progenitors. The present work uses optic pathways of rat and mouse as well‐characterized systems for the study of gliogenesis. plp gene expression was monitored with a combination of reverse transcriptase polymerase chain reaction, in situ hybridization, and immunostaining with antibodies to different PLP peptide sequences, combined with O‐2A lineage markers. In tissue sections, hybridizing cells were detected initially in the proximal optic tracts between E18 and birth and thereafter progressively in the chiasm and optic nerves. Small unbranched cells expressing DM‐20 but not myelin basic protein (MBP) and probably representing progenitors were detectable by immunostaining in similar locations. With increasing postnatal ages, cells representing maturing oligodendrocytes which co‐label for PLP and MBP are present in the optic pathways. In vitro analysis of freshly dissociated cells from premyelinated optic nerve demonstrated that the plp gene is expressed in some O‐2A progenitor cells as well as mature oligodendrocytes. We also present evidence that increase in expression of the plp gene along the O‐2A lineage differentiation is not progressive but that downregulation at the proligodendroblast (O4+/O1‐) stage probably occurs. We suggest that progenitors express the dm‐20 isoform while oligodendrocytes express predominantly the plp isoform. Not all progenitors express the plp gene at the times studied, indicating that the presence of DM‐20 is either transitory in individual cells or that only a sub‐population is involved. The function of DM‐20 at this early stage of the oligodendrocyte lineage has yet to be determined. © 1996 Wiley‐Liss, Inc.

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Molecular Biology and Neurogenetics of Myelin Proteolipid Protein

Cited by 5 publications

References 25 publications

Oligodendroglia Regulate the Regional Expansion of Axon Caliber and Local Accumulation of Neurofilaments during Development Independently of Myelin Formation

Oligodendroglia Regulate the Regional Expansion of Axon Caliber and Local Accumulation of Neurofilaments during Development Independently of Myelin Formation

Charcot-Marie-Tooth Disease and Related Inherited Myelin Disorders: Molecular Genetics and Implications for Gene Therapy

Evidence that some oligodendrocyte progenitors in the developing optic pathway express the plp gene

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