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1 Chapter 31 Formation and Maintenance of Myelin Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved.

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Presentation on theme: "1 Chapter 31 Formation and Maintenance of Myelin Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved."— Presentation transcript:

1 1 Chapter 31 Formation and Maintenance of Myelin Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved.

2 2 FIGURE 31-1: Development of the Schwann cell lineage. The initial neural crest cell expresses ErbB3, the p75 NGF receptor, L1 and N-cadherin. This cell develops into the Schwann cell progenitor when it begins to express AP2α and Sox10. The Schwann cell progenitor cell continues to express several neural crest markers and starts expressing cadherin 19, desert hedgehog (DHH), brain fatty acid– binding protein (BFABP), and low levels of P0, PLP and PMP22. This cell then matures to an immature Schwann cell that has lost expression of N-cadherin and cadherin 19 and increases expression of GFAP and S100β. Increased expression of the transcription factors Krox20/Egr2, BRN2 and Oct6/Scip lead to myelination by the myelinating Schwann cell. These cells have lost GFAP and S100β expression and they increased myelin protein expression. In Schwann cells that become nonmyelinating Schwann cells, myelin gene expression ceases and GFAP and S100 remain. This figure is based on figures and data from multiple studies, in particular (Jessen & Mirsky 2005). Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved.

3 3 FIGURE 31-2: Myelin formation in the peripheral nervous system. (A) The Schwann cell has surrounded the axon but the external surfaces of the plasma membrane have not yet fused in the mesaxon. (B) The mesaxon has fused into a five-layered structure and spiraled once around the axon. (C) A few layers of myelin have formed but are not completely compacted. Note the cytoplasm trapped in zones where the cytoplasmic membrane surfaces have not yet fused. (D) Compact myelin showing only a few layers for the sake of clarity. Note that Schwann cell cytoplasm forms a ring both inside and outside of the sheath. (Adapted with permission from Norton, W. T. The myelin sheath. In E. S. Goldensohn and S. H. Appel (eds), Scientific Approaches to Clinical Neurology. Philadelphia: Lea & Febiger, 1977, pp. 259–298.) Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved.

4 4 FIGURE 31-3: Development of the oligodendrocyte lineage. The bipolar oligodendrocyte progenitor cell expresses the Olig1/2, Sox10 and Nkx2.2 transcription factors indicative of this lineage and early inhibitory transcription factors that maintain its progenitor state as it migrates through the nervous system. It expresses PDGF receptor alpha and NG2 proteoglycan through its early development to the late progenitor stage, which starts to express early myelin antigens such as O4. Inhibitory transcription factors are downregulated as the Tcf4 transcription factor and the myelin antigen O1 start to be expressed. Tcf4 is then downregulated and several other transcription factors are expressed that are essential for the myelinating phenotype. At this stage, high levels of myelin proteins are expressed. Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved.

5 5 FIGURE 31-4: Premyelinating and myelinating oligodendrocytes in vivo. Representative images of (A) premyelinating oligodendrocytes from P6 mouse cortex, labeled with EGFP (in Plp -EGFP mice (Mallon et al., 2002) and PLP (Texas Red) or (B) a myelinating oligodendrocyte from mature mouse striatum labeled with EGFP (in Plp -EGFP mice). (Figure 4B reproduced from Mallon et al., 2002). Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved.

6 6 FIGURE 31-5: NRG/ErbB signaling that regulates both active myelination and termination of myelination in Schwann cells. (A) During the active phase of myelination of peripheral nerves, axonal expression of neuregulin-1 activates erbB2 and erbB3 receptors on Schwann cells and signals through the PI3K-Akt pathway to initiate myelin production. Neuregulin also induces an increase in Dlg1 levels, presumably by preventing its ubiquitination and subsequent degradation. (B) As non-ubiquitinated Dlg1 accumulates, it stabilizes PTEN, reducing its proteosomal degradation, and the number of Dlg1-PTEN complexes increases. This reduces Akt activity and terminates active myelination. (Figure and Figure legend from Macklin, 2010.) Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved.

7 7 TABLE 31-1: Some Spontaneously Occurring Animal Mutants Affecting Myelin Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved.


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