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Cold Spring Harbor Perspectives in... Jun 2015Myelinated nerve fibers are essential for the rapid propagation of action potentials by saltatory conduction. They form as the result of reciprocal interactions between... (Review)
Review
Myelinated nerve fibers are essential for the rapid propagation of action potentials by saltatory conduction. They form as the result of reciprocal interactions between axons and Schwann cells. Extrinsic signals from the axon, and the extracellular matrix, drive Schwann cells to adopt a myelinating fate, whereas myelination reorganizes the axon for its role in conduction and is essential for its integrity. Here, we review our current understanding of the development, molecular organization, and function of myelinating Schwann cells. Recent findings into the extrinsic signals that drive Schwann cell myelination, their cognate receptors, and the downstream intracellular signaling pathways they activate will be described. Together, these studies provide important new insights into how these pathways converge to activate the transcriptional cascade of myelination and remodel the actin cytoskeleton that is critical for morphogenesis of the myelin sheath.
Topics: Action Potentials; Epigenesis, Genetic; Humans; Myelin Sheath; Nerve Fibers, Myelinated; Schwann Cells; Signal Transduction; Transcription, Genetic
PubMed: 26054742
DOI: 10.1101/cshperspect.a020529 -
The Journal of Physiology Jul 2016Nerve injury triggers the conversion of myelin and non-myelin (Remak) Schwann cells to a cell phenotype specialized to promote repair. Distal to damage, these repair... (Review)
Review
Nerve injury triggers the conversion of myelin and non-myelin (Remak) Schwann cells to a cell phenotype specialized to promote repair. Distal to damage, these repair Schwann cells provide the necessary signals and spatial cues for the survival of injured neurons, axonal regeneration and target reinnervation. The conversion to repair Schwann cells involves de-differentiation together with alternative differentiation, or activation, a combination that is typical of cell type conversions often referred to as (direct or lineage) reprogramming. Thus, injury-induced Schwann cell reprogramming involves down-regulation of myelin genes combined with activation of a set of repair-supportive features, including up-regulation of trophic factors, elevation of cytokines as part of the innate immune response, myelin clearance by activation of myelin autophagy in Schwann cells and macrophage recruitment, and the formation of regeneration tracks, Bungner's bands, for directing axons to their targets. This repair programme is controlled transcriptionally by mechanisms involving the transcription factor c-Jun, which is rapidly up-regulated in Schwann cells after injury. In the absence of c-Jun, damage results in the formation of a dysfunctional repair cell, neuronal death and failure of functional recovery. c-Jun, although not required for Schwann cell development, is therefore central to the reprogramming of myelin and non-myelin (Remak) Schwann cells to repair cells after injury. In future, the signalling that specifies this cell requires further analysis so that pharmacological tools that boost and maintain the repair Schwann cell phenotype can be developed.
Topics: Animals; Humans; Myelin Sheath; Nerve Regeneration; Nervous System Diseases; Schwann Cells
PubMed: 26864683
DOI: 10.1113/JP270874 -
The Journal of Clinical Investigation Apr 2016Nerves enable cancer progression, as cancers have been shown to extend along nerves through the process of perineural invasion, which carries a poor prognosis....
Nerves enable cancer progression, as cancers have been shown to extend along nerves through the process of perineural invasion, which carries a poor prognosis. Furthermore, the innervation of some cancers promotes growth and metastases. It remains unclear, however, how nerves mechanistically contribute to cancer progression. Here, we demonstrated that Schwann cells promote cancer invasion through direct cancer cell contact. Histological evaluation of murine and human cancer specimens with perineural invasion uncovered a subpopulation of Schwann cells that associates with cancer cells. Coculture of cancer cells with dorsal root ganglion extracts revealed that Schwann cells direct cancer cells to migrate toward nerves and promote invasion in a contact-dependent manner. Upon contact, Schwann cells induced the formation of cancer cell protrusions in their direction and intercalated between the cancer cells, leading to cancer cell dispersion. The formation of these processes was dependent on Schwann cell expression of neural cell adhesion molecule 1 (NCAM1) and ultimately promoted perineural invasion. Moreover, NCAM1-deficient mice showed decreased neural invasion and less paralysis. Such Schwann cell behavior reflects normal Schwann cell programs that are typically activated in nerve repair but are instead exploited by cancer cells to promote perineural invasion and cancer progression.
Topics: Animals; CD56 Antigen; Cell Line, Tumor; Coculture Techniques; Humans; Mice; Mice, Nude; NIH 3T3 Cells; Neoplasm Invasiveness; Neoplasms, Experimental; Schwann Cells
PubMed: 26999607
DOI: 10.1172/JCI82658 -
Cells & Development Jun 2021Schwann cell precursors (SCPs) are a transient population in the embryo, closely associated with nerves along which they migrate into the periphery of the body. Long... (Review)
Review
Schwann cell precursors (SCPs) are a transient population in the embryo, closely associated with nerves along which they migrate into the periphery of the body. Long considered to be progenitors that only form Schwann cells-the myelinating cells of nerves, current evidence suggests that SCPs have much broader developmental potential. Indeed, different cell marking techniques employed over the past 20 years have identified multiple novel SCP derivatives throughout the body. It is now clear that SCPs represent a multipotent progenitor population, which also display a level of plasticity in response to injury. Moreover, they originate from multiple origins in the embryo and may reflect several distinct subpopulations in terms of molecular identity and fate. Here we review SCP origins, derivatives and plasticity in development, growth and repair.
Topics: Animals; Cell Differentiation; Cell Lineage; Humans; Models, Biological; Neuronal Plasticity; Schwann Cells; Stem Cells
PubMed: 33994354
DOI: 10.1016/j.cdev.2021.203686 -
Developmental Neurobiology Jul 2021Schwann cells play a critical role in the development of the peripheral nervous system (PNS), establishing important relationships both with the extracellular milieu and... (Review)
Review
Schwann cells play a critical role in the development of the peripheral nervous system (PNS), establishing important relationships both with the extracellular milieu and other cell types, particularly neurons. In this review, we discuss various Schwann cell interactions integral to the proper establishment, spatial arrangement, and function of the PNS. We include signals that cascade onto Schwann cells from axons and from the extracellular matrix, bidirectional signals that help to establish the axo-glial relationship and how Schwann cells in turn support the axon. Further, we speculate on how Schwann cell interactions with other components of the developing PNS ultimately promote the complete construction of the peripheral nerve.
Topics: Axons; Cell Communication; Neuroglia; Peripheral Nervous System; Schwann Cells
PubMed: 32281247
DOI: 10.1002/dneu.22744 -
Cells & Development Dec 2021Schwann cell precursors (SCPs) are a transient population in the embryo, closely associated with nerves along which they migrate into the periphery of the body. Long... (Review)
Review
Schwann cell precursors (SCPs) are a transient population in the embryo, closely associated with nerves along which they migrate into the periphery of the body. Long considered to be progenitors that only form Schwann cells-the myelinating cells of nerves, current evidence suggests that SCPs have much broader developmental potential. Indeed, different cell marking techniques employed over the past 20 years have identified multiple novel SCP derivatives throughout the body. It is now clear that SCPs represent a multipotent progenitor population, which also display a level of plasticity in response to injury. Moreover, they originate from multiple origins in the embryo and may reflect several distinct subpopulations in terms of molecular identity and fate. Here we review SCP origins, derivatives and plasticity in development, growth and repair.
Topics: Cell Differentiation; Embryo, Mammalian; Schwann Cells
PubMed: 34456178
DOI: 10.1016/j.cdev.2021.203729 -
Current Opinion in Cell Biology Dec 1996Recent studies of Schwann cell differentiation in vivo and in vitro have provided new insights into determinative signal transduction events both at the cell surface and... (Review)
Review
Recent studies of Schwann cell differentiation in vivo and in vitro have provided new insights into determinative signal transduction events both at the cell surface and in the nucleus. Several polypeptide growth factors and their receptors, most notably the neuregulins and receptors of the ErbB family, have been implicated in the specification of cell fate, the control of precursor cell proliferation, and the regulation of programmed cell death during both early and late Schwann cell differentiation. Our understanding of the transcriptional control of Schwann cell development, particularly by the POU protein SCIP and the zinc-finger protein Krox-20, has been advanced by transgenic, knockout, and expression studies.
Topics: Animals; Cell Differentiation; Schwann Cells
PubMed: 8939676
DOI: 10.1016/s0955-0674(96)80090-1 -
Glia Mar 2019Schwann cells respond to nerve injury by cellular reprogramming that generates cells specialized for promoting regeneration and repair. These repair cells clear... (Review)
Review
Schwann cells respond to nerve injury by cellular reprogramming that generates cells specialized for promoting regeneration and repair. These repair cells clear redundant myelin, attract macrophages, support survival of damaged neurons, encourage axonal growth, and guide axons back to their targets. There are interesting parallels between this response and that found in other tissues. At the cellular level, many other tissues also react to injury by cellular reprogramming, generating cells specialized to promote tissue homeostasis and repair. And at the molecular level, a common feature possessed by Schwann cells and many other cells is the injury-induced activation of genes associated with epithelial-mesenchymal transitions and stemness, differentiation states that are linked to cellular plasticity and that help injury-induced tissue remodeling. The number of signaling systems regulating Schwann cell plasticity is rapidly increasing. Importantly, this includes mechanisms that are crucial for the generation of functional repair Schwann cells and nerve regeneration, although they have no or a minor role elsewhere in the Schwann cell lineage. This encourages the view that selective tools can be developed to control these particular cells, amplify their repair supportive functions and prevent their deterioration. In this review, we discuss the emerging similarities between the injury response seen in nerves and in other tissues and survey the transcription factors, epigenetic mechanisms, and signaling cascades that control repair Schwann cells, with emphasis on systems that selectively regulate the Schwann cell injury response.
Topics: Animals; Axons; Disease Models, Animal; Epithelial-Mesenchymal Transition; Myelin Sheath; Nerve Regeneration; Neuronal Plasticity; Schwann Cells
PubMed: 30632639
DOI: 10.1002/glia.23532 -
Advances in Experimental Medicine and... 2019Increasing studies have demonstrated multiple signaling molecules responsible for oligodendrocytes and Schwann cells development such as migration, differentiation,... (Review)
Review
Increasing studies have demonstrated multiple signaling molecules responsible for oligodendrocytes and Schwann cells development such as migration, differentiation, myelination, and axo-glial interaction. However, complicated roles in these events are still poorly understood. This chapter focuses on well established intracellular signaling transduction and recent topics that control myelination and are elucidated from accumulating evidences. The underlying molecular mechanisms, which involved in membrane trafficking through small GTPase Arf6 and its activator cytohesins, demonstrate the crosstalk between well established intracellular signaling transduction and a new finding signaling pathway in glial cells links to physiological phenotype and essential role in peripheral nerve system (PNS). Since Arf family proteins affect the expression levels of myelin protein zero (MPZ) and Krox20, which is a transcription factor regulatory factor in early developmental stages of Schwann cells, Arf proteins likely to be key regulator for Schwann cells development. Herein, we discuss how intracellular signaling transductions in Schwann cells associate with myelination in CNS and PNS.
Topics: Humans; Myelin Sheath; Neuroglia; Oligodendroglia; Remyelination; Schwann Cells; Signal Transduction
PubMed: 31760634
DOI: 10.1007/978-981-32-9636-7_1 -
Developmental Biology Dec 2018Schwann cell precursors (SCPs) are multipotent embryonic progenitors covering all developing peripheral nerves. These nerves grow and navigate with unprecedented... (Review)
Review
Schwann cell precursors (SCPs) are multipotent embryonic progenitors covering all developing peripheral nerves. These nerves grow and navigate with unprecedented precision, delivering SCP progenitors to almost all locations in the embryonic body. Within specific developing tissues, SCPs detach from nerves and generate neuroendocrine cells, autonomic neurons, mature Schwann cells, melanocytes and other cell types. These properties of SCPs evoke resemblances between them and their parental population, namely, neural crest cells. Neural crest cells are incredibly multipotent migratory cells that revolutionized the course of evolution in the lineage of early chordate animals. Given this similarity and recent data, it is possible to hypothesize that proto-neural crest cells are similar to SCPs spreading along the nerves. Here, we review the multipotency of SCPs, the signals that govern them, their potential therapeutic value, SCP's embryonic origin and their evolutionary connections. We dedicate this article to the memory of Wilhelm His, the father of the microtome and "Zwischenstrang", currently known as the neural crest.
Topics: Animals; Cell Differentiation; Cell Movement; Chordata; Melanocytes; Multipotent Stem Cells; Neural Crest; Neurogenesis; Neuronal Plasticity; Neurons; Schwann Cells; Stem Cells; Vertebrates
PubMed: 29454705
DOI: 10.1016/j.ydbio.2018.02.008