Redundant Myelin Sheaths and Other Ultrastructural Features of the Toad Cerebellum

Rosenbluth, Jack

doi:10.1083/jcb.28.1.73

Cited by 138 publications

(53 citation statements)

References 31 publications

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“…Such aberrant myelin outfoldings were also found occasionally in control CNS white matter. The sporadic presence of such structures during normal development has been reported previously in amphibian cerebellum (Rosenbluth, 1966). Their genesis is unclear but may be related to the deregulation of molecular events that accompany the early stages of axon ensheathment, in particular those associated with the removal of cytoplasm in areas in which the glial lamellae undergo compaction.…”

Section: Ablation Of Cdc42 Results In the Formation Of Aberrant Myelimentioning

confidence: 84%

Cdc42 and Rac1 Signaling Are Both Required for and Act Synergistically in the Correct Formation of Myelin Sheaths in the CNS

Thurnherr¹,

Benninger²,

Wu³

et al. 2006

J. Neurosci.

125

126

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The formation of myelin sheaths in the CNS is the result of a complex series of events involving oligodendrocyte progenitor cell (OPC) proliferation, directed migration, and the morphological changes associated with axon ensheathment and myelination. To examine the role of Rho GTPases in oligodendrocyte biology, we have used a conditional tissue-specific gene-targeting approach. Ablation of Cdc42 in cells of the oligodendrocyte lineage did not affect OPC proliferation, directed migration, or in vitro differentiation, but it led to the formation of a unique and stage-specific myelination phenotype. This was characterized by the extraordinary enlargement of the inner tongue of the oligodendrocyte process and concomitant formation of a myelin outfolding as a result of abnormal accumulation of cytoplasm in this region. Ablation of Rac1 also resulted in the abnormal accumulation of cytoplasm in the inner tongue of the oligodendrocyte process, and we provide genetic evidence that rac1 synergizes with cdc42 in a gene dosage-dependent way to regulate myelination.

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Section: Ablation Of Cdc42 Results In the Formation Of Aberrant Myelimentioning

confidence: 84%

Cdc42 and Rac1 Signaling Are Both Required for and Act Synergistically in the Correct Formation of Myelin Sheaths in the CNS

Thurnherr¹,

Benninger²,

Wu³

et al. 2006

J. Neurosci.

125

126

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“…Although there was a small increase in the number of redundant myelin profiles (Fig. 6 Ab, arrow and asterisks), such profiles are well known to occur in the normal CNS as well, although somewhat less frequently (Rosenbluth, 1966). Paranodal loops that indent the axon and axoglial junctions with regularly spaced transverse bands were normal in all cases (Fig.…”

Section: Oligodendrocyte Differentiation and Myelination In Differentmentioning

confidence: 82%

Mice with Conditional Inactivation of Fibroblast Growth Factor Receptor-2 Signaling in Oligodendrocytes Have Normal Myelin But Display Dramatic Hyperactivity when Combined with Cnp1 Inactivation

Kaga¹,

Shoemaker²,

Furusho³

et al. 2006

J. Neurosci.

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Fibroblast growth factor receptors (Fgfr) comprise a widely expressed family of developmental regulators implicated in oligodendrocyte (OL) maturation of the CNS. Fgfr2 is expressed by OLs in myelinated fiber tracks. In vitro, Fgfr2 is highly upregulated during OL terminal differentiation, and its activation leads to enhanced growth of OL processes and the formation of myelin-like membranes. To investigate the in vivo function of Fgfr2 signaling by myelinating glial cells, we inactivated the floxed Fgfr2 gene in mice that coexpress Cre recombinase (cre) as a knock-in gene into the OL-specific 2Ј,3Ј-cyclic nucleotide phosphodiesterase (Cnp1) locus. Surprisingly, no obvious defects were detected in brain development of these conditional mutants, including the number of OLs, the onset and extent of myelination, the ultrastructure of myelin, and the expression level of myelin proteins. However, unexpectedly, a subset of these conditional Fgfr2 knock-out mice that are homozygous for cre and therefore are also Cnp1 null, displayed a dramatic hyperactive behavior starting at ϳ2 weeks of age. This hyperactivity was abolished by treatment with dopamine receptor antagonists or catecholamine biosynthesis inhibitors, suggesting that the symptoms involve a dysregulation of the dopaminergic system. Although the molecular mechanisms are presently unknown, this novel mouse model of hyperactivity demonstrates the potential involvement of OLs in neuropsychiatric disorders, as well as the nonpredictable role of genetic interactions in the behavioral phenotype of mice.

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“…5C), and for deformation of the myelin sheath profiles, resulting in redundant folds (Fig. 5C) (38). In addition, in the myelin sheaths of RPTP␤ Ϫ/Ϫ animals, cytoplasm-containing lamellae can be found extending into juxtaparanodal regions (Fig.…”

Section: Normal Migration Of Mesencephalic Neurons In Rptp␤mentioning

confidence: 96%

No Obvious Abnormality in Mice Deficient in Receptor Protein Tyrosine Phosphatase β

Harroch¹,

Palmeri²,

Rosenbluth

et al. 2000

Molecular and Cellular Biology

100

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The development of neurons and glia is governed by a multitude of extracellular signals that control protein tyrosine phosphorylation, a process regulated by the action of protein tyrosine kinases and protein tyrosine phosphatases (PTPs). Receptor PTP␤ (RPTP␤; also known as PTP) is expressed predominantly in the nervous system and exhibits structural features common to cell adhesion proteins, suggesting that this phosphatase participates in cell-cell communication. It has been proposed that the three isoforms of RPTP␤ play a role in regulation of neuronal migration, neurite outgrowth, and gliogenesis. To investigate the biological functions of this PTP, we have generated mice deficient in RPTP␤. RPTP␤-deficient mice are viable, are fertile, and showed no gross anatomical alterations in the nervous system or other organs. In contrast to results of in vitro experiments, our study demonstrates that RPTP␤ is not essential for neurite outgrowth and node formation in mice. The ultrastructure of nerves of the central nervous system in RPTP␤-deficient mice suggests a fragility of myelin. However, conduction velocity was not altered in RPTP␤-deficient mice. The normal development of neurons and glia in RPTP␤-deficient mice demonstrates that RPTP␤ function is not necessary for these processes in vivo or that loss of RPTP␤ can be compensated for by other PTPs expressed in the nervous system.Protein tyrosine phosphatases (PTPs), in concert with protein tyrosine kinases (PTKs), regulate signal transduction pathways by tyrosine phosphorylation and dephosphorylation. PTPs comprise a structurally diverse family of enzymes. One group of PTPs exhibit structural features that are also common to cell surface receptors and cell adhesion molecules (CAMs), suggesting that these receptors may play a role in cell-cell communication (4,43). These receptor-like PTPs (RPTPs) are composed of an extracellular domain, a single transmembrane domain, and a cytoplasmic portion that contains one or two tyrosine phosphatase domains. RPTP␤ (also known as PTP) and RPTP␥ are two members of a subfamily of RPTPs that contain a region in their extracellular domains that has sequence homology to the enzyme carbonic anhydrase (CAH) (2,3,24,25). In both RPTP␤ and RPTP␥, the CAH domain is followed by a fibronectin domain type III repeat and by a long unique sequence termed the spacer domain. Three different isoforms of RPTP␤ are expressed as a result of alternative mRNA splicing: a short and a long form that differ by the presence of a stretch of 860 amino acid residues in the spacer domain and a secreted form composed of only the extracellular domain of RPTP␤, also known as 3F8 proteoglycan or phosphacan. Both transmembrane RPTP␤s and the phosphacan isoform are predominantly expressed as chondroitin sulfate proteoglycans.Previous studies have suggested a role for RPTP␤ in gliogenesis and neuron-glial cell interaction, neurite outgrowth, and neuronal migration, as well as in regeneration after injury (21,26,43).

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Redundant Myelin Sheaths and Other Ultrastructural Features of the Toad Cerebellum

Cited by 138 publications

References 31 publications

Cdc42 and Rac1 Signaling Are Both Required for and Act Synergistically in the Correct Formation of Myelin Sheaths in the CNS

Cdc42 and Rac1 Signaling Are Both Required for and Act Synergistically in the Correct Formation of Myelin Sheaths in the CNS

Mice with Conditional Inactivation of Fibroblast Growth Factor Receptor-2 Signaling in Oligodendrocytes Have Normal Myelin But Display Dramatic Hyperactivity when Combined with Cnp1 Inactivation

No Obvious Abnormality in Mice Deficient in Receptor Protein Tyrosine Phosphatase β

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