Internodal myelination during development quantitated using X-ray diffraction

Agrawal, Deepika; Hawk, Rachel; Avila, Robin; Inouye, Hideyo; Kirschner, Daniel A.

doi:10.1016/j.jsb.2009.06.019

Cited by 34 publications

(43 citation statements)

References 33 publications

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“…We treated control (MRF FL/FL ) and iCKO (MRF FL/FL ; PLP-CreERT) mice with 4OHT at 8 weeks of age ( Fig. 1 B), by which time the majority of developmental myelination is established (Agrawal et al, 2009). Semiquantitative RT-PCR analysis of RNA isolated from spinal cords confirmed that, in the absence of 4OHT administration, both control and iCKO mice expressed the full-length MRF transcript.…”

Section: Continuous Oligodendrocyte Expression Of Mrf Is Required To mentioning

confidence: 76%

Myelin Gene Regulatory Factor Is Required for Maintenance of Myelin and Mature Oligodendrocyte Identity in the Adult CNS

et al. 2012

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Although the transcription factors required for the generation of oligodendrocytes and CNS myelination during development have been relatively well established, it is not known whether continued expression of the same factors is required for the maintenance of myelin in the adult. Here, we use an inducible conditional knock-out strategy to investigate whether continued oligodendrocyte expression of the recently identified transcription factor myelin gene regulatory factor (MRF) is required to maintain the integrity of myelin in the adult CNS. Genetic ablation of MRF in mature oligodendrocytes within the adult CNS resulted in a delayed but severe CNS demyelination, with clinical symptoms beginning at 5 weeks and peaking at 8 weeks after ablation of MRF. This demyelination was accompanied by microglial/macrophage infiltration and axonal damage. Transcripts for myelin genes, such as proteolipid protein, MAG, MBP, and myelin oligodendrocyte glycoprotein, were rapidly downregulated after ablation of MRF, indicating an ongoing requirement for MRF in the expression of these genes. Subsequently, a proportion of the recombined oligodendrocytes undergo apoptosis over a period of weeks. Surviving oligodendrocytes gradually lose the expression of mature markers such as CC1 antigen and their association with myelin, without reexpressing oligodendrocyte progenitor markers or reentering the cell cycle. These results demonstrate that ongoing expression of MRF within the adult CNS is critical to maintain mature oligodendrocyte identity and the integrity of CNS myelin.

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Section: Continuous Oligodendrocyte Expression Of Mrf Is Required To mentioning

confidence: 76%

Myelin Gene Regulatory Factor Is Required for Maintenance of Myelin and Mature Oligodendrocyte Identity in the Adult CNS

et al. 2012

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“…We detected low levels of myocilin protein in mouse sciatic nerve as early as P3, the earliest analyzed stage, with expression levels increasing to reach approximately adult levels by P21, a time when myelination is almost completed (24) (Fig. 1).…”

Section: Myocilin Interacts With Several Nodal Proteins Within the Scmentioning

confidence: 89%

Myocilin Mediates Myelination in the Peripheral Nervous System through ErbB2/3 Signaling

Kwon¹,

Johnson²,

Margetis³

et al. 2013

Journal of Biological Chemistry

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Background: Myocilin, a secreted glaucoma-associated protein, is detected in the sciatic nerve, but its function there is not clear. Results: Myocilin null mutation leads to defects in the myelination of sciatic nerve acting through the ErbB2/ErbB3 receptor. Conclusion: Myocilin is a novel player in sciatic nerve myelination. Significance: This is the first demonstration of myocilin involvement in myelination.

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“…The unit of the myelin multi-lamellar ultrastructure is shown in Figure 1b. It is made of the stacking of (i) one cytoplasmatic apposition (cyt), (ii) one lipidic membrane (lpg), (iii) one extracellular apposition (ext), and (iv) another lipidic mambrane (lpg) [3][4][5] …”

Section: Axon Orientation Fluctuationsmentioning

confidence: 99%

“…It has a periodic multi-lamellar structure, whose unit is made up of the repetition of four layers: cytoplasmic apposition of Schwann cells (cyt), lipidic membrane (lpg) extracellular apposition of Schwann cells (ext) and another lipidic membrane (lpg). The available information about the myelin layers has been extracted from measurements performed by space averaged laboratory X-Ray Diffraction (XRD) [3][4][5][6], electron microscopy (EM) [6,7] and neutron diffraction [8].…”

Section: Introductionmentioning

confidence: 99%

Correlated Disorder in Myelinated Axons Orientational Geometry and Structure

et al. 2017

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While the ultrastructure of myelin is considered a quasi-crystalline stable system, nowadays its multiscale complex dynamics appear to play a key role in its functionality, degeneration and repair processes following neurological diseases and trauma. In this work, we investigated the fluctuation of the myelin supramolecular assembly by measuring the spatial distribution of orientation fluctuations of axons in a Xenopus Laevis sciatic nerve associated with nerve functionality. To this end, we used scanning micro X-ray diffraction (SµXRD), a non-invasive technique that has already been applied to other heterogeneous systems presenting complex geometries from microscale to nanoscale. We found that the orientation of the spatial fluctuations of fresh axons show a Levy flight distribution, which is a clear indication of correlated disorder. We found that the Levy flight distribution was missing in the aged nerve prepared in an unfresh state. This result shows that the spatial distribution of axon orientation fluctuations in unfresh nerve state loses the correlated disorder and assumes a random disorder behavior. This work provides a deeper understanding of the ultrastructure-function nerve relation and paves the way for the study of other materials and biomaterials using the SµXRD technique to detect fluctuations in their supramolecular structure.

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Internodal myelination during development quantitated using X-ray diffraction

Cited by 34 publications

References 33 publications

Myelin Gene Regulatory Factor Is Required for Maintenance of Myelin and Mature Oligodendrocyte Identity in the Adult CNS

Myelin Gene Regulatory Factor Is Required for Maintenance of Myelin and Mature Oligodendrocyte Identity in the Adult CNS

Myocilin Mediates Myelination in the Peripheral Nervous System through ErbB2/3 Signaling

Correlated Disorder in Myelinated Axons Orientational Geometry and Structure

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