Novel Signals Controlling Embryonic Schwann Cell Development, Myelination and Dedifferentiation

Department of Cell and Developmental Biology, University College London, London, UK.
Journal of the Peripheral Nervous System (Impact Factor: 2.76). 07/2008; 13(2):122-35. DOI: 10.1111/j.1529-8027.2008.00168.x
Source: PubMed


Immature Schwann cells found in perinatal rodent nerves are generated from Schwann cell precursors (SCPs) that originate from the neural crest. Immature Schwann cells generate the myelinating and non-myelinating Schwann cells of adult nerves. When axons degenerate following injury, Schwann cells demyelinate, proliferate and dedifferentiate to assume a molecular phenotype similar to that of immature cells, a process essential for successful nerve regeneration. Increasing evidence indicates that Schwann cell dedifferentiation involves activation of specific receptors, intracellular signalling pathways and transcription factors in a manner analogous to myelination. We have investigated the roles of Notch and the transcription factor c-Jun in development and after nerve transection. In vivo, Notch signalling regulates the transition from SCP to Schwann cell, times Schwann cell generation, controls Schwann cell proliferation and acts as a brake on myelination. Notch is elevated in injured nerves where it accelerates the rate of dedifferentiation. Likewise, the transcription factor c-Jun is required for Schwann cell proliferation and death and is down-regulated by Krox-20 on myelination. Forced expression of c-Jun in Schwann cells prevents myelination, and in injured nerves, c-Jun is required for appropriate dedifferentiation, the re-emergence of the immature Schwann cell state and nerve regeneration. Thus, both Notch and c-Jun are negative regulators of myelination. The growing realisation that myelination is subject to negative as well as positive controls and progress in molecular identification of negative regulators is likely to impact on our understanding of demyelinating disease and mechanisms that control nerve repair.

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Available from: Kristján R Jessen, Oct 07, 2015
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    • "During this stage c-Jun, Sox2 and Pax3 are also activated (Doddrell et al., 2012; Jessen and Mirsky, 2008; Kim et al., 2013; Lutz and Barres, 2014; Mirsky et al., 2008 Parkinson et al., 2008; Patodia and Raivich, 2012; Yang et al., 2012). At this time point, SC release chemokines and cytokines to attract haematological immune cells such as macrophages and T-cells (Jessen and Mirsky, 2008; Kato et al., 2013; Lutz and Barres, 2014; Martini et al., 2008; Mietto et al., 2013; Ydens et al., 2013). "
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    DESCRIPTION: Dissertation project using Cre-loxP Merlin-null mice to assess macrophage infiltration and proliferation after peripheral nerve injury
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    • "Peripheral nerve myelination is achieved by the plasma membrane of Schwann cells (SCs), the sole glial cells of peripheral nerves, wrapping around axons during perinatal and early postnatal development. In fact, the myelin sheath is a notable outcome of the differentiation of SCs [2, 3, 4]. Once the myelin sheath is formed and matured postnatally, the integrity of the myelin sheath is maintained throughout life unless the nerve is physically or chemically damaged. "
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    ABSTRACT: Schwann cells (SCs) in the peripheral nerves myelinate axons during postnatal development to allow saltatory conduction of nerve impulses. Well-organized structures of myelin sheathes are maintained throughout life unless nerves are insulted. After peripheral nerve injury, unidentified signals from injured nerves drive SC dedifferentiation into an immature state. Dedifferentiated SCs participate in axonal regeneration by producing neurotrophic factors and removing degenerating nerve debris. In this review, we focus on the role of mitogen activated protein kinase family proteins (MAP kinases) in SC dedifferentiation. In addition, we will highlight neuregulin 1 and the transcription factor c-jun as upstream and downstream signals for MAP kinases in SC responses to nerve injury.
    06/2014; 23(2):130-7. DOI:10.5607/en.2014.23.2.130
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    • "At W9, the cochlear duct consisted of one full turn, the future basal turn. To identify PGCs, we immunostained for SOX10 (a nuclear marker for PGCs regardless of developmental stage [35], [36]), S100B (a cytoplasmic marker expressed in animals by immature and mature Schwann cells but not by Schwann cell precursors [37], [38]) and TUBB3 (a general marker of SGNs) (Fig. 2A–H). In the CN, abundant SOX10+/S100B+ PGCs were detected surrounding essentially all central processes (Fig. 2E). "
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    ABSTRACT: The adult human cochlea contains various types of peripheral glial cells that envelop or myelinate the three different domains of the spiral ganglion neurons: the central processes in the cochlear nerve, the cell bodies in the spiral ganglia, and the peripheral processes in the osseous spiral lamina. Little is known about the distribution, lineage separation and maturation of these peripheral glial cells in the human fetal cochlea. In the current study, we observed peripheral glial cells expressing SOX10, SOX9 and S100B as early as 9 weeks of gestation (W9) in all three neuronal domains. We propose that these cells are the common precursor to both mature Schwann cells and satellite glial cells. Additionally, the peripheral glial cells located along the peripheral processes expressed NGFR, indicating a phenotype distinct from the peripheral glial cells located along the central processes. From W12, the spiral ganglion was gradually populated by satellite glial cells in a spatiotemporal gradient. In the cochlear nerve, radial sorting was accomplished by W22 and myelination started prior to myelination of the peripheral processes. The developmental dynamics of the peripheral glial cells in the human fetal cochlea is in support of a neural crest origin. Our study provides the first overview of the distribution and maturation of peripheral glial cells in the human fetal cochlea from W9 to W22.
    PLoS ONE 01/2014; 9(1):e88066. DOI:10.1371/journal.pone.0088066 · 3.23 Impact Factor
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