scholarly journals Nectin-like proteins mediate axon–Schwann cell interactions along the internode and are essential for myelination

2007 ◽  
Vol 178 (5) ◽  
pp. 861-874 ◽  
Author(s):  
Patrice Maurel ◽  
Steven Einheber ◽  
Jolanta Galinska ◽  
Pratik Thaker ◽  
Isabel Lam ◽  
...  
Keyword(s):  
Nervous System ◽  
Cell Differentiation ◽  
Schwann Cell ◽  
Peripheral Nervous System ◽  
Schwann Cells ◽  
Molecular Complexes ◽  
Hairpin Rna ◽  
Nodal Region ◽  
Short Hairpin ◽  
Schwann Cell Differentiation

Axon–glial interactions are critical for the induction of myelination and the domain organization of myelinated fibers. Although molecular complexes that mediate these interactions in the nodal region are known, their counterparts along the internode are poorly defined. We report that neurons and Schwann cells express distinct sets of nectin-like (Necl) proteins: axons highly express Necl-1 and -2, whereas Schwann cells express Necl-4 and lower amounts of Necl-2. These proteins are strikingly localized to the internode, where Necl-1 and -2 on the axon are directly apposed by Necl-4 on the Schwann cell; all three proteins are also enriched at Schmidt-Lanterman incisures. Binding experiments demonstrate that the Necl proteins preferentially mediate heterophilic rather than homophilic interactions. In particular, Necl-1 on axons binds specifically to Necl-4 on Schwann cells. Knockdown of Necl-4 by short hairpin RNA inhibits Schwann cell differentiation and subsequent myelination in cocultures. These results demonstrate a key role for Necl-4 in initiating peripheral nervous system myelination and implicate the Necl proteins as mediators of axo–glial interactions along the internode.

scholarly journals Peripheral nervous system plasmalogens regulate Schwann cell differentiation and myelination

2014 ◽  
Vol 124 (6) ◽  
pp. 2560-2570 ◽  
Author(s):  
Tiago Ferreira da Silva ◽  
Jessica Eira ◽  
André T. Lopes ◽  
Ana R. Malheiro ◽  
Vera Sousa ◽  
...  
Keyword(s):  
Nervous System ◽  
Cell Differentiation ◽  
Schwann Cell ◽  
Peripheral Nervous System ◽  
Schwann Cell Differentiation

scholarly journals Dependence on Schwann Cell-Derived Laminin-γ1 Differentiates Early Lymphoid and Myeloid Development

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 37-37
Author(s):  
Kristin Komnick ◽  
Jennifer May ◽  
Pouneh Kermani ◽  
Sreemanti Basu ◽  
Irene Hernandez ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Nervous System ◽  
Schwann Cell ◽  
Peripheral Nerve ◽  
Peripheral Nervous System ◽  
Schwann Cells ◽  
Adrenergic Nerve ◽  
Spleen Size ◽  
Mouse Line ◽  
Myeloid Development

Blood cell production is regulated by peripheral nerve fibers that innervate the bone marrow. However, little is known about the development or maintenance of hematopoietic innervation. Schwann cells (SCs) are the primary axon 'support cells' of the peripheral nervous system (PNS), and abnormal SC development is sufficient to impair peripheral nerve function. SCs are also the primary repair cell for the PNS which makes them an attractive therapeutic target for normalization of drug or malignancy-induced 'hematopoietic neuropathy'. We hypothesized that neural regulation of hematopoiesis is dependent on SC development. To test this hypothesis, we used the Myelin Protein Zero-Cre (MP0-Cre); Lamc1fl/fl mouse line in which laminin-γ1 expression is deleted from SC precursors and their progeny1. Early SC maturation is dependent on autocrine SC precursor-derived molecules such as laminin-γ1. SC differentiation arrests prior to axon sorting and ensheathment in MP0-Cre; Lamc1fl/fl mice, and causes a global peripheral neuropathy that persists throughout the lifetime of the animal. Preliminary hematopoietic analysis of 'steady state' MP0-Cre; Lamc1fl/fl and littermate control mice has shown the following: (1) MP0-Cre; Lamc1fl/fl bone marrow is innervated, and Cre-mediated gene recombination occurs in cells immunophenotypically consistent with SCs throughout the peripheral nervous system, including those in the bone marrow; (2) MP0-Cre; Lamc1fl/fl mice are lymphopenic but not neutropenic; (3) MP0-Cre; Lamc1fl/fl mice have significantly reduced spleen size and cellularity; and (4) MP0-Cre; Lamc1fl/fl bone marrow has an ~50% reduction in Lin-Sca-1+Kit+(LSK) cells (measured as a percentage of the Lin- compartment of the bone marrow). These results are consistent with earlier work by our groups in which we found that global Lamc1 gene deletion in adult mice induced peripheral blood lymphopenia, reduced spleen size, and a niche-dependent reduction of lymphoid progenitor and precursor cells that was secondary to increased lymphoid precursor cell apoptosis and reduced proliferation (UBC-CreERT2; Lamc1fl/fl mouse line). As with the SC-specific laminin-γ1 deficient mice, myelopoiesis was preserved in the UBC-CreERT2; Lamc1fl/fl mice. Based on results from MP0-Cre; Lamc1fl/fl and UBC-CreERT2; Lamc1fl/fl mice, we conclude that early lymphoid but not myeloid development requires laminin-γ1 expression by MP0-Cre-targetted niche cells, i.e. Schwann Cells. Our results are consistent with reports from other labs that hematopoietic sympathetic neuropathy promotes aberrant myeloid expansion at the expense of lymphopoiesis2. Going forward, we will determine whether lymphopoietic development is dependent on global versus laminin-specific SC-derived cues, and whether these signals are transmitted directly between SCs and lymphoid biased HSPCs or indirectly via other components of the hematopoietic niche. We anticipate that this line of investigation will provide molecular insights and pharmacologic targets for prevention and or normalization of the 'hematopoietic neuropathy' induced by diabetes, aging, neurotoxic chemotherapies and myeloid malignancies. REFERENCES: 1 Yu, W. M., Feltri, M. L., Wrabetz, L., Strickland, S. & Chen, Z. L. Schwann cell-specific ablation of laminin gamma1 causes apoptosis and prevents proliferation. J Neurosci25, 4463-4472, doi:10.1523/JNEUROSCI.5032-04.2005 (2005). 2 Maryanovich, M. et al. Adrenergic nerve degeneration in bone marrow drives aging of the hematopoietic stem cell niche. Nat Med24, 782-791, doi:10.1038/s41591-018-0030-x (2018). Disclosures No relevant conflicts of interest to declare.

scholarly journals SoxD transcription factor deficiency in Schwann cells delays myelination in the developing peripheral nervous system

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ella Ittner ◽  
Anna C. Hartwig ◽  
Olga Elsesser ◽  
Hannah M. Wüst ◽  
Franziska Fröb ◽  
...  
Keyword(s):  
Nervous System ◽  
Schwann Cell ◽  
Peripheral Nervous System ◽  
Schwann Cells ◽  
Terminal Differentiation ◽  
Factor Deficiency ◽  
Schwann Cell Development ◽  
The Central Nervous System ◽  
Brain And Spinal Cord

AbstractThe three SoxD proteins, Sox5, Sox6 and Sox13, represent closely related transcription factors with important roles during development. In the developing nervous system, SoxD proteins have so far been primarily studied in oligodendroglial cells and in interneurons of brain and spinal cord. In oligodendroglial cells, Sox5 and Sox6 jointly maintain the precursor state, interfere with terminal differentiation, and thereby ensure the proper timing of myelination in the central nervous system. Here we studied the role of SoxD proteins in Schwann cells, the functional counterpart of oligodendrocytes in the peripheral nervous system. We show that Schwann cells express Sox5 and Sox13 but not Sox6. Expression was transient and ceased with the onset of terminal differentiation. In mice with early Schwann cell-specific deletion of both Sox5 and Sox13, embryonic Schwann cell development was not substantially affected and progressed normally into the promyelinating stage. However, there was a mild and transient delay in the myelination of the peripheral nervous system of these mice. We therefore conclude that SoxD proteins—in stark contrast to their action in oligodendrocytes—promote differentiation and myelination in Schwann cells.

scholarly journals Essential and distinct roles for cdc42 and rac1 in the regulation of Schwann cell biology during peripheral nervous system development

2007 ◽  
Vol 177 (6) ◽  
pp. 1051-1061 ◽  
Author(s):  
Yves Benninger ◽  
Tina Thurnherr ◽  
Jorge A. Pereira ◽  
Sven Krause ◽  
Xunwei Wu ◽  
...  
Keyword(s):  
Nervous System ◽  
Schwann Cell ◽  
Peripheral Nervous System ◽  
Schwann Cells ◽  
Rho Gtpases ◽  
Cell Biology ◽  
System Development ◽  
Nervous System Development ◽  
Conditional Gene Targeting ◽  
Radial Sorting

During peripheral nervous system (PNS) myelination, Schwann cells must interpret extracellular cues to sense their environment and regulate their intrinsic developmental program accordingly. The pathways and mechanisms involved in this process are only partially understood. We use tissue-specific conditional gene targeting to show that members of the Rho GTPases, cdc42 and rac1, have different and essential roles in axon sorting by Schwann cells. Our results indicate that although cdc42 is required for normal Schwann cell proliferation, rac1 regulates Schwann cell process extension and stabilization, allowing efficient radial sorting of axon bundles.

scholarly journals Antibodies to the L1 adhesion molecule inhibit Schwann cell ensheathment of neurons in vitro.

1989 ◽  
Vol 109 (6) ◽  
pp. 3095-3103 ◽  
Author(s):  
B Seilheimer ◽  
E Persohn ◽  
M Schachner
Keyword(s):  
Cell Differentiation ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Adhesion Molecule ◽  
Neuronal Cell ◽  
Dorsal Root Ganglion Neurons ◽  
Neural Adhesion Molecule ◽  
Ganglion Neurons ◽  
Schwann Cell Differentiation

To investigate whether neural adhesion molecules are involved in neuron-induced Schwann cell differentiation, cocultures of pure dorsal root ganglion neurons, and Schwann cells were maintained in the presence of antibodies to evaluate possible perturbing effects. Several parameters characteristic of differentiating Schwann cells were studied, such as transition of spindle-shaped to flattened, i.e., more epithelioid morphology, association with neuronal cell bodies, ensheathment of neurites, production of basal lamina and collagen fibrils, and expression of the myelin associated glycoprotein (MAG). A complete ablation of Schwann cell differentiation in all features studied was seen with antibodies to the neural adhesion molecule L1. Antibodies to N-CAM did not reduce the association of Schwann cells with neurites but abolished the interdigitation of Schwann cell processes into neurite bundles, while leaving the other parameters studied unaffected. Fab fragments of antibodies to J1, MAG, and mouse liver membranes did not interfere with the manifestation of any of these parameters. None of the antibodies changed incorporation of [3H]thymidine into Schwann cells.

scholarly journals Four Seasons for Schwann Cell Biology, Revisiting Key Periods: Development, Homeostasis, Repair, and Aging

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1887
Author(s):  
Gabriela Sardella-Silva ◽  
Bruno Siqueira Mietto ◽  
Victor Túlio Ribeiro-Resende
Keyword(s):  
Nervous System ◽  
Schwann Cell ◽  
Peripheral Nervous System ◽  
Schwann Cells ◽  
Cell Biology ◽  
System Development ◽  
High Energy ◽  
Nervous System Development ◽  
Loss Of Function ◽  
Essential Information

Like the seasons of the year, all natural things happen in stages, going through adaptations when challenged, and Schwann cells are a great example of that. During maturation, these cells regulate several steps in peripheral nervous system development. The Spring of the cell means the rise and bloom through organized stages defined by time-dependent regulation of factors and microenvironmental influences. Once matured, the Summer of the cell begins: a high energy stage focused on maintaining adult homeostasis. The Schwann cell provides many neuron-glia communications resulting in the maintenance of synapses. In the peripheral nervous system, Schwann cells are pivotal after injuries, balancing degeneration and regeneration, similarly to when Autumn comes. Their ability to acquire a repair phenotype brings the potential to reconnect axons to targets and regain function. Finally, Schwann cells age, not only by growing old, but also by imposed environmental cues, like loss of function induced by pathologies. The Winter of the cell presents as reduced activity, especially regarding their role in repair; this reflects on the regenerative potential of older/less healthy individuals. This review gathers essential information about Schwann cells in different stages, summarizing important participation of this intriguing cell in many functions throughout its lifetime.

scholarly journals Differentiation of axon-related Schwann cells in vitro. I. Ascorbic acid regulates basal lamina assembly and myelin formation.

1987 ◽  
Vol 105 (2) ◽  
pp. 1023-1034 ◽  
Author(s):  
C F Eldridge ◽  
M B Bunge ◽  
R P Bunge ◽  
P M Wood
Keyword(s):  
Ascorbic Acid ◽  
Cell Differentiation ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Basal Lamina ◽  
Defined Medium ◽  
Acid Oxidase ◽  
Myelin Formation ◽  
Schwann Cell Differentiation ◽  
Cells Cultured

Rat Schwann cells cultured with dorsal root ganglion neurons in a serum-free defined medium fail to ensheathe or myelinate axons or assemble basal laminae. Replacement of defined medium with medium that contains human placental serum (HPS) and chick embryo extract (EE) results in both basal lamina and myelin formation. In the present study, the individual effects of HPS and EE on basal lamina assembly and on myelin formation by Schwann cells cultured with neurons have been examined. Some batches of HPS were unable to promote myelin formation in the absence of EE, as assessed by quantitative evaluation of cultures stained with Sudan black; such HPS also failed to promote basal lamina assembly, as assessed by immunofluorescence using antibodies against laminin, type IV collagen, and heparan sulfate proteoglycan. The addition of EE or L-ascorbic acid with such HPS led to the formation of large quantities of myelin and to the assembly of basal laminae. Pretreatment of EE with ascorbic acid oxidase abolished the EE activity, whereas trypsin did not. Other batches of HPS were found to promote both basal lamina and myelin formation in the absence of either EE or ascorbic acid. Ascorbic acid oxidase treatment or dialysis of these batches of HPS abolished their ability to promote Schwann cell differentiation, whereas the subsequent addition of ascorbic acid restored that ability. Ascorbic acid in the absence of serum was relatively ineffective in promoting either basal lamina or myelin formation. Fetal bovine serum was as effective as HPS in allowing ascorbic acid (and several analogs but not other reducing agents) to manifest its ability to promote Schwann cell differentiation. We suggest that ascorbic acid promotes Schwann cell myelin formation by enabling the Schwann cell to assemble a basal lamina, which is required for complete differentiation.

scholarly journals Egr2-guided histone H2B monoubiquitination is required for peripheral nervous system myelination

2020 ◽  
Vol 48 (16) ◽  
pp. 8959-8976 ◽  
Author(s):  
Hannah M Wüst ◽  
Amélie Wegener ◽  
Franziska Fröb ◽  
Anna C Hartwig ◽  
Florian Wegwitz ◽  
...  
Keyword(s):  
Nervous System ◽  
Schwann Cell ◽  
Peripheral Nervous System ◽  
Schwann Cells ◽  
Target Genes ◽  
Expression Patterns ◽  
Chromatin Modification ◽  
E3 Ligase ◽  
Global Gene Expression ◽  
Histone H2b

Abstract Schwann cells are the nerve ensheathing cells of the peripheral nervous system. Absence, loss and malfunction of Schwann cells or their myelin sheaths lead to peripheral neuropathies such as Charcot-Marie-Tooth disease in humans. During Schwann cell development and myelination chromatin is dramatically modified. However, impact and functional relevance of these modifications are poorly understood. Here, we analyzed histone H2B monoubiquitination as one such chromatin modification by conditionally deleting the Rnf40 subunit of the responsible E3 ligase in mice. Rnf40-deficient Schwann cells were arrested immediately before myelination or generated abnormally thin, unstable myelin, resulting in a peripheral neuropathy characterized by hypomyelination and progressive axonal degeneration. By combining sequencing techniques with functional studies we show that H2B monoubiquitination does not influence global gene expression patterns, but instead ensures selective high expression of myelin and lipid biosynthesis genes and proper repression of immaturity genes. This requires the specific recruitment of the Rnf40-containing E3 ligase by Egr2, the central transcriptional regulator of peripheral myelination, to its target genes. Our study identifies histone ubiquitination as essential for Schwann cell myelination and unravels new disease-relevant links between chromatin modifications and transcription factors in the underlying regulatory network.

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