The neuromuscular junction (NMJ) is a tripartite synapse comprised of an α-motor neuron (the presynapse), extrafusal muscle fiber (the postsynapse), and specialized synaptic glia called perisynaptic Schwann cells (PSCs) or terminal Schwann cells. Due to its large size and accessibility, extensive research of the NMJ has been essential to the discovery of the fundamental mechanisms that govern synaptic function, including the concepts of neurotransmitter release, quantal transmission, and active zones, among others (Katz and Miledi, 1967; Fatt and Katz, 1952; Sealock et al., 1989; Sobel et al., 1979; Sobel et al., 1977; Sanes and Lichtman, 1999; Darabid et al., 2014; Katz and Miledi, 1966; Robertson, 1956; Changeux et al., 1970; Godfrey et al., 1984; Jennings et al., 1993; Lwebuga-Mukasa et al., 1976; Nitkin et al., 1987; Porter and Froehner, 1983). Likewise, the concept of glia that exist primarily to support synapse function, and thus the realization that synapses are tripartite, has its origins at the NMJ (Robertson, 1956; Couteaux, 1960; Kang et al., 2007; Zuo et al., 2004; Griffin and Thompson, 2008; Boeke, 1949; Heuser and Reese, 1973; Miledi and Slater, 1968; Miledi and Slater, 1970; Peper et al., 1974; Astrow et al., 1994; Astrow et al., 1998; Reynolds and Woolf, 1992; Young et al., 2005). PSCs surround the NMJ where they are closely associated with its pre- and postsynaptic components (Griffin and Thompson, 2008; Ko and Robitaille, 2015; Darabid et al., 2014). In addition to providing trophic support for the NMJ (Griffin and Thompson, 2008; Ko and Robitaille, 2015; Darabid et al., 2014; Reddy et al., 2003), PSCs have been shown to guide motor axon innervation and synaptogenesis (Reddy et al., 2003; Trachtenberg and Thompson, 1997; Koirala et al., 2000; O'Malley et al., 1999; Barik et al., 2016), support compensatory axonal sprouting (Astrow et al., 1994; Reynolds and Woolf, 1992; Son and Thompson, 1995; Love and Thompson, 1998), participate in synaptic pruning (Griffin and Thompson, 2008; Lee et al., 2017; Smith et al., 2013; Darabid et al., 2013), and detect and modulate cholinergic transmission (Ko and Robitaille, 2015; Jahromi et al., 1992; Reist and Smith, 1992; Robitaille, 1995; Robitaille et al., 1997; Rochon et al., 2001).

While great progress has been made in understanding the cellular and physiological characteristics of PSCs, very little is known about the molecular composition of these cells (Ko and Robitaille, 2015). This has been due to the absence of a cell-specific molecular marker with which PSCs can be identified, isolated, and genetically manipulated. This has hindered examinations of the processes of PSC development, differentiation and turnover. Additionally, isolation and targeting of PSCs for interrogation of molecular function in vivo and in vitro has not been possible. Therefore, the discovery of markers specific to PSCs is necessary to advance our understanding of PSCs, and synaptic glia in general, on multiple fronts.

A growing number of molecular markers that recognize subsets of glial cells throughout the nervous system have been identified (Jäkel and Dimou, 2017). Therefore, we explored the possibility that a unique combination of glial cell markers could be used to distinguish PSCs. We have found that PSCs can be identified by the combined expression of the calcium-binding protein B (S100β) (Brockes et al., 1979; Perez and Moore, 1968) and neuron-glia antigen-2 (NG2) (Stallcup, 1981; Bergles et al., 2010) genes. We utilized this unique molecular fingerprint to create a transgenic mouse that enables visualization and isolation of PSCs in a cell specific manner. This genetic model will help overcome obstacles to understanding the cellular and molecular rules that govern PSC function at NMJs during development, following injury, in old age, and in diseases, such as Amyotrophic Lateral Sclerosis (ALS).

To identify unique markers for PSCs, we examined the expression of genes shown to be co-expressed with well-established markers of Schwann cells in a subset of glial cells in the central nervous system in PSCs. We focused on NG2 for the following reasons: 1) it has been found to be co-expressed with S100β, a classical marker of all Schwann cells, in a subset of glial cells in the developing brain (Matthias et al., 2003; Hachem et al., 2005; Vives et al., 2003; Moshrefi-Ravasdjani et al., 2017; Platel et al., 2009); 2) published data show that it is expressed in skeletal muscles and labels pericytes and neural progenitor cells (Birbrair et al., 2013a; Birbrair et al., 2013b). To determine if NG2 is expressed by PSCs, we examined whole-mounted extensor digitorum longus (EDL) muscles from NG2-dsRed mice (Zhu et al., 2008). We observed widespread distribution of NG2-dsRed postive cells in the EDL muscle, including a distinct subset of cells located specifically at the NMJ and with a similar morphology as PSCs (Figure 1C). To determine if NG2 is expressed in PSCs we generated a transgenic mouse line (referred herein as S100β-GFP;NG2-dsRed; Figure 1A) by crossing the NG2-dsRed line with the S100β-GFP mouse line in which the S100β promoter drives expression of GFP in all Schwann cells (Zuo et al., 2004). As expected, in the resulting S100β-GFP;NG2-dsRed double transgenic mouse line, dsRed labeled all NG2 positive cells (referred herein as NG2-dsRed⁺) and GFP labeled all Schwann cells (referred herein as S100β-GFP⁺) (Figure 1B–C) in skeletal muscles. However, we found a select subset of glia positive for both S100β-GFP and NG2-dsRed specifically located at the NMJ (yellow cells in Figure 1D). Based on the location and morphology of the cell body and its elaborations, we concluded that PSCs are the only cells expressing both S100β-GFP and NG2-dsRed in skeletal muscles.

Figure 1

Download asset Open asset

We next evaluated whether the S100β-GFP;NG2-dsRed mouse line serves as a reliable model to study PSCs and their roles at NMJs. In healthy young adult muscle, we observed the same number of PSCs at NMJs in the EDL muscle of S100β-GFP and S100β-GFP;NG2-dsRed mice (Figure 2A–C). The morphology of PSCs also appeared to be indistinguishable between the two transgenic lines. In addition, the morphology of NMJs, as assessed by fragmentation of nicotinic acetylcholine receptor (nAChR) clusters, is unchanged in S100β-GFP;NG2-dsRed mice compared to S100β-GFP and wild type mice (Figure 2A,B,D). Thus, the co-expression of S100β-GFP and NG2-dsRed does not appear to cause apparent deleterious changes on either PSCs or the postsynaptic region revealed by nAChRs. However, it remains possible that co-expression of these markers in PSCs may disrupt the presynapse and biophysical properties of the NMJ. If so, we hypothesize that such changes would be minor given that S100β-GFP;NG2-dsRed mice are outwardly indistinguishable when compared to S100β-GFP and wild type mice.

Figure 2

Download asset Open asset

We next assessed if S100β-GFP;NG2-dsRed mice could also be used to study PSCs at degenerating and regenerating NMJs. First, we examined expression of NG2-dsRed and S100β-GFP after crushing the fibular nerve (Dalkin et al., 2016). In this injury model, motor axons completely retract within 1 day and return to reinnervate vacated postsynaptic sites by 7 days post-injury in young adult mice. Similar to healthy uninjured EDL muscles (Figure 2E), NG2-dsRed and S100β-GFP were found co-expressed exclusively in PSCs at 4d and 7d post-injury (Figure 2F–G). Second, we crossed the SOD1^G93A mouse line, (Gurney et al., 1994) a model of ALS shown to exhibit significant degeneration of NMJs (Moloney et al., 2014), with S100β-GFP;NG2-dsRed mice and examined the expression pattern of NG2-dsRed and S100β-GFP in the EDL during the symptomatic stage (P120). We again found NG2-dsRed and S100β-GFP co-expressed only in PSCs in the EDL of P120 SOD1^G93A;S100β-GFP;NG2-dsRed mice (Figure 2H). Together, these data strongly indicate that this genetic labeling approach can be deployed to study the synaptic glia of the NMJ in a manner previously not possible in healthy and stressed NMJs.

To determine the relationship between NG2 expression and PSC differentiation, we analyzed NG2 expression in S100β-GFP⁺ Schwann cells during the course of NMJ development in the EDL muscle of S100β-GFP;NG2-dsRed mice (Figure 3A and Figure 3—figure supplement 1). We observed the presence of S100β-GFP⁺ cells at the NMJ as early as embryonic day 15 (E15) with 100% of NMJs having at least one S100β-GFP⁺ cell by post-natal day 9 (Figure 3A,B). During the embryonic developmental stages, we observed that NMJs are exclusively populated by S100β-GFP⁺ cells that do not express NG2-dsRed (Figure 3C). At post-natal day 0 (P0), however, we observed NG2-dsRed expression in a small subset of S100β-GFP⁺ cells (Figure 3A,C). Notably, the proportion of NMJs with S100β-GFP⁺;NG2-dsRed⁺ cells sharply increased between the ages of P0 and P9, coinciding with the period of NMJ maturation in mouse skeletal muscles (Figure 3C). By P21, when NMJ maturation in mice is near completion (Sanes and Lichtman, 1999), we observed S100β-GFP⁺;NG2-dsRed⁺ cells to be exclusively present at NMJs (Figure 3C). At this age, the number of S100β-GFP⁺;NG2-dsRed⁺ PSCs reached an average of 2.3 per NMJ and this remained unchanged in healthy young adult mice (Figure 3A,D). To confirm that dsRed expression from the NG2 promoter denotes the temporal and spatial transcriptional control of the NG2 gene in S100β-GFP;NG2-dsRed mice, we immunostained for NG2 protein. We found NG2 protein present at mature NMJs but not in NMJs of E18 mice with IHC (Figure 3—figure supplement 2). Thus, the induced expression of NG2 during the course of NMJ development in Schwann cells located proximally to the NMJ provides further evidence that NG2 is a marker of mature, differentiated S100β⁺ PSCs. It is possible that PSCs upregulate NG2 during development in order to restrict motor axon growth at the NMJ (Filous et al., 2014). Induced NG2 expression during NMJ development along with the constant presence of S100β-GFP⁺ cells (S100β-GFP⁺ or S100β-GFP⁺;NG2-dsRed⁺) and absence of single labeled NG2-dsRed+ cells at NMJs at every observed developmental time point (Figure 3B,C) strongly support previous studies indicating that PSCs originate from Schwann cells (Lee et al., 2017).

Figure 3 with 2 supplements see all

Download asset Open asset

To gain insights into the rules that govern the distribution of PSCs at NMJs we compared PSC density in EDL, soleus, and diaphragm muscles to determine if PSC density is similar across muscles with varying NMJ sizes, fiber types and functional demands. Here, we observed similar PSC densities in each muscle type (Figure 4—figure supplement 1), suggesting that the number of PSCs directly correlates with the size of the NMJ and not the functional characteristics or fiber type composition of the muscles with which they are associated.

We next examined the spatial distribution of PSCs at the NMJ using the Nearest Neighbor (NN) analysis. This analysis measures the linear distance between neighboring cells in order to determine the regularity of spacing (Wassle and Riemann, 1978; Cook, 1996), quantified using the regularity index. In this analysis, randomly distributed groups of cells yield a nearest neighbor regularity index (NNRI) of 1.91 while those with nonrandom, regularly ordered distributions yield higher NNRI values (Reese and Keeley, 2015; Figure 4A). We found that the spacing of PSCs yielded high NNRI values and thus maintained ordered, non-random distributions at NMJs in the EDL muscle of adult mice. Moreover, this ordered distribution was maintained regardless of the overall number of PSCs at a given NMJ (Figure 4B–D). These observations are in accord with a published study indicating that PSCs occupy distinct territories at adult NMJs (Brill et al., 2011). In addition, these data strongly suggest that presynaptic, postsynaptic, and/or PSC-PSC mechanisms of communication dictate the spatial distribution of PSCs.

Figure 4 with 1 supplement see all

Download asset Open asset

The ability to distinguish PSCs from all other Schwann cells makes it possible to identify genes that are either preferentially or specifically expressed in PSCs. We deployed fluorescence-activated cell sorting (FACS) to separately isolate double labeled S100β-GFP⁺;NG2-dsRed⁺ PSCs, single-labeled S100β-GFP⁺ Schwann cells, and single-labeled NG2-dsRed⁺ cells (including α-SMA pericytes and Tuj1⁺ precursor cells [Birbrair et al., 2013b]) from juvenile (P15-P22) S100β-GFP;NG2-dsRed transgenic mice. We then utilized RNA-Sequencing (RNA Seq) to compare the transcriptional profile of PSCs with the other two groups (Figure 5A). Light microscopy and expression analysis of GFP and dsRed using quantitative PCR (qPCR) confirmed that only cells of interest were sorted (Figure 5A–B). This analysis revealed a unique transcriptional profile for PSCs (Figure 5C). Notably, we found 567 genes enriched in PSCs that were not previously recognized to be associated with PSCs, glial cells or synapses (Supplementary file 1) using Ingenuity Pathway Analysis (IPA). We also found a number of genes preferentially expressed by PSCs with known roles at synapses (Mozer and Sandstrom, 2012; Fox and Umemori, 2006; Rafuse et al., 2000; Ranaivoson et al., 2019; Shapiro et al., 2007; Peng et al., 2010; Supplementary file 1). Providing additional insights about the function of PSCs, IPA revealed synaptogenesis, glutamate receptor, and axon guidance signaling as top canonical pathways under transcriptional regulation (Figure 5D).

Figure 5

Download asset Open asset

We next cross-referenced our transcriptomic data with a list of genes compiled from published studies indicating enrichment or functional roles in PSCs (Young et al., 2005; Reynolds and Woolf, 1992; Robitaille, 1995; Robitaille et al., 1997; Rochon et al., 2001; Georgiou and Charlton, 1999; Trachtenberg and Thompson, 1996; Morris et al., 1999; Woldeyesus et al., 1999; Riethmacher et al., 1997; Personius et al., 2016; Park et al., 2017; Pinard et al., 2003; Descarries et al., 1998; Hess et al., 2007; Heredia et al., 2018; Darabid et al., 2018; Musarella et al., 2006; De Winter et al., 2006; Feng and Ko, 2008; Yang et al., 2001; Petrov et al., 2014; Robitaille et al., 1996; Gorlewicz et al., 2009; Wright et al., 2009). This analysis identified 27 genes expressed in isolated S100β-GFP⁺;NG2-dsRed⁺ PSCs that were previously shown to be associated with PSCs (Table 1). These included genes involved in detection and modulation of synaptic activity such as adenosine (Robitaille, 1995; Rochon et al., 2001), P2Y (Robitaille, 1995; Heredia et al., 2018; Darabid et al., 2018), acetylcholine (Robitaille et al., 1997; Petrov et al., 2014; Wright et al., 2009) and glutamate receptors (Pinard et al., 2003), Butyrylcholinesterase (BChE) (Petrov et al., 2014), and L-type calcium channels (Robitaille et al., 1996). Additionally, genes involved in NMJ development, synaptic pruning, and maintenance including agrin, 2',3'-cyclic nucleotide 3' phosphodiesterase (CNP) (Georgiou and Charlton, 1999), Erb-b2 receptor tyrosine kinase 2 (Erbb2) (Trachtenberg and Thompson, 1996; Morris et al., 1999; Woldeyesus et al., 1999), Erbb3 (Trachtenberg and Thompson, 1996; Riethmacher et al., 1997) GRB2-associated protein 1 (Gab1) (Park et al., 2017), myelin-associated glycoprotein (MAG) (Georgiou and Charlton, 1999), and myelin protein zero (Mpz) (Georgiou and Charlton, 1999) were detected in PSCs.

We deployed quantitative PCR (qPCR) to validate preferential expression of select genes in PSCs. To do so, we obtained RNA from S100β-GFP⁺;NG2-dsRed⁺ PSCs, single-labeled S100β-GFP⁺ Schwann cells, and single-labeled NG2-dsRed⁺ cells isolated using FACS from juvenile S100β-GFP;NG2-dsRed transgenic mice. We examined eight genes identified by RNA seq as being highly enriched in PSCs. This included newly identified genes (Ajap1, Col20a1, FoxD3, Nrxn1, PDGFa, and Pdlim4) and genes previously shown to be enriched (BChE [Petrov et al., 2014] and NCAM1 [Covault and Sanes, 1986]) in PSCs (Figure 5E). Validating RNA-Seq findings, qPCR analysis showed that all eight genes are highly enriched in PSCs compared to all other cell types isolated via FACS (Figure 5E). Additionally, immunostaining showed that NG2, a novel PSC-enriched gene identified by RNA-Seq, is concentrated at the NMJ (Figure 3—figure supplement 2).

We have discovered a unique combination of molecular markers that allows us to specifically visualize, isolate, interrogate the transcriptome, and potentially alter the molecular composition of PSCs. We have shown that NG2 is specifically expressed by S100β-GFP⁺ PSCs but not myelinating S100β-GFP⁺ Schwann cells and thus the combined expression of S100β and NG2 is a unique molecular marker of PSCs in skeletal muscle. Providing further evidence that NG2 is a marker of differentiated PSCs, we have demonstrated that Schwann cells induce expression of NG2 shortly after they arrive at the NMJ during maturation of the synapse. However, the means by which the induced expression of NG2 is part of a program to establish and/or further specify PSC identity in Schwann cells at the NMJ, through activation of the NG2 promoter, remains to be determined.

We utilized FACS to isolate S100β-GFP⁺;NG2-dsRed⁺ PSCs from skeletal muscle to analyze the PSC transcriptome. To our knowledge this is the first time that the transcriptome of PSCs, or any other type of glial cell that associates exclusively with synapses, has been characterized. This analysis reveals expression of a number of genes that have been previously implicated in modulation of synaptic activity, synaptic pruning, and synaptic maintenance by PSCs. We identified a number of novel genes that are highly expressed in PSCs but not Schwann cells or NG2⁺ cells. These genes have the potential to assist PSC research by serving as molecular markers that can be utilized for PSC-specific genetic manipulations, PSC ablation, and isolation of PSCs for cell culture and molecular analysis. We verified a number of these with qPCR and IHC. This analysis, therefore, reveals a unique gene expression signature that distinguishes PSCs from all other Schwann cells.

While the role of the majority of genes found enriched in PSCs at the neuromuscular synapse remains to be determined, it is worth noting that many have been shown to play key roles in neuronal circuits in the central nervous system and in cell-cell communication. This is the case for NG2 which has been shown to terminate axonal growth in glial scars in the spinal cord (Filous et al., 2014). Therefore, it is possible that NG2 is utilized by PSCs to tile, and thus occupy unique territories, and prevent motor axons from developing sprouts that extend beyond the postsynaptic partner. Supporting this possibility, we have found that the NG2 promoter is active in some PSCs at P0 (Figure 3C), a time when motor axon nerve endings at NMJs undergo rapid morphological changes (Sanes and Lichtman, 1999; Sanes and Lichtman, 2001). The progressive activation of the NG2 promoter in PSCs is complete by P9 (Figure 3C), which coincides with the elimination of extranumeral axons innervating the same postsynaptic site in mice (Sanes and Lichtman, 1999; Sanes and Lichtman, 2001). Therefore, PSCs may utilize NG2 to promote the maturation of the presynaptic region and thus the NMJ. Furthermore, PSCs may utilize NG2 to repel each other as they tile during development to occupy unique territories at the NMJ (Brill et al., 2011).

With these tools, it is now possible to determine which cellular and molecular determinants are critical for PSC differentiation, maturation, and function at the NMJ. It will also allow us to ascertain the contribution of PSCs to NMJ repair following injury and NMJ degeneration during normal aging and the progression of neuromuscular diseases, such as Amyotrophic Lateral Sclerosis (ALS) and Spinal Muscular Atrophy (SMA). Our strategy of specifically labeling synaptic glia, using a combination of protein markers uniquely expressed in this cell type, may serve as a springboard for unprecedented approaches for studying not only PSC function at the NMJ, but also synapse-associated glia throughout the CNS. Indeed, we have observed subsets of astrocytes in the brain that co-express both S100β and NG2, as has been previously reported in the context of a lineage tracing analysis (Deloulme et al., 2004). Future studies will determine the generality of our approach in discerning the functional roles of synaptic glia in the development, maintenance, and function of select synapses.

RNA-Seq data has been deposited in NCBI GEO and all other data is available in the main text or the supplementary materials. The GEO accession number for this dataset is GSE152774.

1. 1. Castro R
   2. Taetzsch T
   3. Vaughan SK
   4. Godbe K
   5. Chappell J
   6. Settlage RE
   7. Valdez G

   (2020) NCBI Gene Expression Omnibus

   ID GSE152774. Synaptic Schwann cells: specific labeling reveals unique cellular and molecular features.

   https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE152774

1. 1. Anders S
   2. Pyl PT
   3. Huber W

   (2015) HTSeq--a Python framework to work with high-throughput sequencing data

   Bioinformatics 31:166–169.

   https://doi.org/10.1093/bioinformatics/btu638

   • PubMed
   • Google Scholar
2. 1. Aronesty E

   (2013) Comparison of sequencing utility programs

   The Open Bioinformatics Journal 7:1–8.

   https://doi.org/10.2174/1875036201307010001

   • Google Scholar
3. 1. Astrow SH
   2. Son YJ
   3. Thompson WJ

   (1994) Differential neural regulation of a neuromuscular junction-associated antigen in muscle fibers and schwann cells

   Journal of Neurobiology 25:937–952.

   https://doi.org/10.1002/neu.480250804

   • PubMed
   • Google Scholar
4. 1. Astrow SH
   2. Qiang H
   3. Ko CP

   (1998) Perisynaptic schwann cells at neuromuscular junctions revealed by a novel monoclonal antibody

   Journal of Neurocytology 27:667–681.

   https://doi.org/10.1023/a:1006916232627

   • PubMed
   • Google Scholar
5. 1. Barik A
   2. Li L
   3. Sathyamurthy A
   4. Xiong WC
   5. Mei L

   (2016) Schwann cells in neuromuscular junction formation and maintenance

   Journal of Neuroscience 36:9770–9781.

   https://doi.org/10.1523/JNEUROSCI.0174-16.2016

   • PubMed
   • Google Scholar
6. 1. Bergles DE
   2. Jabs R
   3. Steinhäuser C

   (2010) Neuron-glia synapses in the brain

   Brain Research Reviews 63:130–137.

   https://doi.org/10.1016/j.brainresrev.2009.12.003

   • PubMed
   • Google Scholar
7. 1. Birbrair A
   2. Zhang T
   3. Wang ZM
   4. Messi ML
   5. Enikolopov GN
   6. Mintz A
   7. Delbono O

   (2013a) Role of pericytes in skeletal muscle regeneration and fat accumulation

   Stem Cells and Development 22:2298–2314.

   https://doi.org/10.1089/scd.2012.0647

   • PubMed
   • Google Scholar
8. 1. Birbrair A
   2. Zhang T
   3. Wang ZM
   4. Messi ML
   5. Enikolopov GN
   6. Mintz A
   7. Delbono O

   (2013b) Skeletal muscle pericyte subtypes differ in their differentiation potential

   Stem Cell Research 10:67–84.

   https://doi.org/10.1016/j.scr.2012.09.003

   • PubMed
   • Google Scholar
9. 1. Boeke J

   (1949) The sympathetic endformation, its synaptology, the interstitial cells, the periterminal network, and its bearing on the neurone theory discussion and critique

   Cells Tissues Organs 8:18–61.

   https://doi.org/10.1159/000140398

   • Google Scholar
10. 1. Brill MS
    2. Lichtman JW
    3. Thompson W
    4. Zuo Y
    5. Misgeld T

    (2011) Spatial constraints dictate glial territories at murine neuromuscular junctions

    Journal of Cell Biology 195:293–305.

    https://doi.org/10.1083/jcb.201108005

    • Google Scholar
11. 1. Brockes JP
    2. Fields KL
    3. Raff MC

    (1979) Studies on cultured rat schwann cells. I. establishment of purified populations from cultures of peripheral nerve

    Brain Research 165:105–118.

    https://doi.org/10.1016/0006-8993(79)90048-9

    • PubMed
    • Google Scholar
12. 1. Changeux JP
    2. Kasai M
    3. Lee CY

    (1970) Use of a snake venom toxin to characterize the cholinergic receptor protein

    PNAS 67:1241–1247.

    https://doi.org/10.1073/pnas.67.3.1241

    • PubMed
    • Google Scholar
13. 1. Cook JE

    (1996) Spatial properties of retinal mosaics: an empirical evaluation of some existing measures

    Visual Neuroscience 13:15–30.

    https://doi.org/10.1017/S0952523800007094

    • PubMed
    • Google Scholar
14. Book

    1. Couteaux R

    (1960) The Structure and Function of Muscle

    Elsevier.

    https://doi.org/10.1016/C2013-0-10402-3

    • Google Scholar
15. 1. Covault J
    2. Sanes JR

    (1986) Distribution of N-CAM in synaptic and extrasynaptic portions of developing and adult skeletal muscle

    The Journal of Cell Biology 102:716–730.

    https://doi.org/10.1083/jcb.102.3.716

    • PubMed
    • Google Scholar
16. 1. Dalkin W
    2. Taetzsch T
    3. Valdez G

    (2016) The fibular nerve injury method: a reliable assay to identify and test factors that repair neuromuscular junctions

    Journal of Visualized Experiments 11:54186.

    https://doi.org/10.3791/54186

    • Google Scholar
17. 1. Darabid H
    2. Arbour D
    3. Robitaille R

    (2013) Glial cells decipher synaptic competition at the mammalian neuromuscular junction

    Journal of Neuroscience 33:1297–1313.

    https://doi.org/10.1523/JNEUROSCI.2935-12.2013

    • PubMed
    • Google Scholar
18. 1. Darabid H
    2. Perez-Gonzalez AP
    3. Robitaille R

    (2014) Neuromuscular synaptogenesis: coordinating partners with multiple functions

    Nature Reviews Neuroscience 15:703–718.

    https://doi.org/10.1038/nrn3821

    • PubMed
    • Google Scholar
19. 1. Darabid H
    2. St-Pierre-See A
    3. Robitaille R

    (2018) Purinergic-Dependent glial regulation of synaptic plasticity of competing terminals and synapse elimination at the neuromuscular junction

    Cell Reports 25:2070–2082.

    https://doi.org/10.1016/j.celrep.2018.10.075

    • PubMed
    • Google Scholar
20. 1. De Winter F
    2. Vo T
    3. Stam FJ
    4. Wisman LA
    5. Bär PR
    6. Niclou SP
    7. van Muiswinkel FL
    8. Verhaagen J

    (2006) The expression of the chemorepellent semaphorin 3A is selectively induced in terminal schwann cells of a subset of neuromuscular synapses that display limited anatomical plasticity and enhanced vulnerability in motor neuron disease

    Molecular and Cellular Neuroscience 32:102–117.

    https://doi.org/10.1016/j.mcn.2006.03.002

    • PubMed
    • Google Scholar
21. 1. Deloulme JC
    2. Raponi E
    3. Gentil BJ
    4. Bertacchi N
    5. Marks A
    6. Labourdette G
    7. Baudier J

    (2004) Nuclear expression of S100B in oligodendrocyte progenitor cells correlates with differentiation toward the oligodendroglial lineage and modulates oligodendrocytes maturation

    Molecular and Cellular Neuroscience 27:453–465.

    https://doi.org/10.1016/j.mcn.2004.07.008

    • PubMed
    • Google Scholar
22. 1. Descarries LM
    2. Cai S
    3. Robitaille R
    4. Josephson EM
    5. Morest DK

    (1998) Localization and characterization of nitric oxide synthase at the frog neuromuscular junction

    Journal of Neurocytology 27:829–840.

    https://doi.org/10.1023/a:1006907531778

    • PubMed
    • Google Scholar
23. 1. Fatt P
    2. Katz B

    (1952) The electric activity of the motor end-plate

    Proc. R. Soc. London. Ser. B, Biol. Sci 140:183–186.

    https://doi.org/10.1098/rspb.1952.0055

    • Google Scholar
24. 1. Feng Z
    2. Ko CP

    (2008) Schwann cells promote synaptogenesis at the neuromuscular junction via transforming growth factor-beta1

    Journal of Neuroscience 28:9599–9609.

    https://doi.org/10.1523/JNEUROSCI.2589-08.2008

    • PubMed
    • Google Scholar
25. 1. Filous AR
    2. Tran A
    3. Howell CJ
    4. Busch SA
    5. Evans TA
    6. Stallcup WB
    7. Kang SH
    8. Bergles DE
    9. Lee SI
    10. Levine JM
    11. Silver J

    (2014) Entrapment via synaptic-like connections between NG2 proteoglycan+ cells and dystrophic axons in the lesion plays a role in regeneration failure after spinal cord injury

    The Journal of Neuroscience 34:16369–16384.

    https://doi.org/10.1523/JNEUROSCI.1309-14.2014

    • PubMed
    • Google Scholar
26. 1. Fox MA
    2. Umemori H

    (2006) Seeking long-term relationship: axon and target communicate to organize synaptic differentiation

    Journal of Neurochemistry 97:1215–1231.

    https://doi.org/10.1111/j.1471-4159.2006.03834.x

    • PubMed
    • Google Scholar
27. 1. Georgiou J
    2. Charlton MP

    (1999) Non-myelin-forming perisynaptic schwann cells express protein zero and myelin-associated glycoprotein

    Glia 27:101–109.

    https://doi.org/10.1002/(SICI)1098-1136(199908)27:2<101::AID-GLIA1>3.0.CO;2-H

    • PubMed
    • Google Scholar
28. 1. Godfrey EW
    2. Nitkin RM
    3. Wallace BG
    4. Rubin LL
    5. McMahan UJ

    (1984) Components of Torpedo electric organ and muscle that cause aggregation of acetylcholine receptors on cultured muscle cells

    The Journal of Cell Biology 99:615–627.

    https://doi.org/10.1083/jcb.99.2.615

    • PubMed
    • Google Scholar
29. 1. Gorlewicz A
    2. Wlodarczyk J
    3. Wilczek E
    4. Gawlak M
    5. Cabaj A
    6. Majczynski H
    7. Nestorowicz K
    8. Herbik MA
    9. Grieb P
    10. Slawinska U
    11. Kaczmarek L
    12. Wilczynski GM

    (2009) CD44 is expressed in non-myelinating schwann cells of the adult rat, and may play a role in neurodegeneration-induced glial plasticity at the neuromuscular junction

    Neurobiology of Disease 34:245–258.

    https://doi.org/10.1016/j.nbd.2009.01.011

    • Google Scholar
30. 1. Griffin JW
    2. Thompson WJ

    (2008) Biology and pathology of nonmyelinating schwann cells

    Glia 56:1518–1531.

    https://doi.org/10.1002/glia.20778

    • PubMed
    • Google Scholar
31. 1. Gurney ME
    2. Pu H
    3. Chiu AY
    4. Dal Canto MC
    5. Polchow CY
    6. Alexander DD
    7. Caliendo J
    8. Hentati A
    9. Kwon YW
    10. Deng HX

    (1994) Motor neuron degeneration in mice that express a human cu,zn superoxide dismutase mutation

    Science 264:1772–1775.

    https://doi.org/10.1126/science.8209258

    • PubMed
    • Google Scholar
32. 1. Hachem S
    2. Aguirre A
    3. Vives V
    4. Marks A
    5. Gallo V
    6. Legraverend C

    (2005) Spatial and temporal expression of S100B in cells of oligodendrocyte lineage

    Glia 51:81–97.

    https://doi.org/10.1002/glia.20184

    • PubMed
    • Google Scholar
33. 1. Heredia DJ
    2. Feng CY
    3. Agarwal A
    4. Nennecker K
    5. Hennig GW
    6. Gould TW

    (2018) Postnatal restriction of Activity-Induced Ca²⁺ Responses to Schwann Cells at the Neuromuscular Junction Are Caused by the Proximo-Distal Loss of Axonal Synaptic Vesicles during Development

    The Journal of Neuroscience 38:8650–8665.

    https://doi.org/10.1523/JNEUROSCI.0956-18.2018

    • PubMed
    • Google Scholar
34. 1. Hess DM
    2. Scott MO
    3. Potluri S
    4. Pitts EV
    5. Cisterni C
    6. Balice-Gordon RJ

    (2007) Localization of TrkC to schwann cells and effects of neurotrophin-3 signaling at neuromuscular synapses

    The Journal of Comparative Neurology 501:465–482.

    https://doi.org/10.1002/cne.21163

    • PubMed
    • Google Scholar
35. 1. Heuser JE
    2. Reese TS

    (1973) Evidence for recycling of synaptic vesicle membrane during transmitter release at the frog neuromuscular junction

    The Journal of Cell Biology 57:315–344.

    https://doi.org/10.1083/jcb.57.2.315

    • PubMed
    • Google Scholar
36. 1. Jahromi BS
    2. Robitaille R
    3. Charlton MP

    (1992) Transmitter release increases intracellular calcium in Perisynaptic schwann cells in situ

    Neuron 8:1069–1077.

    https://doi.org/10.1016/0896-6273(92)90128-Z

    • PubMed
    • Google Scholar
37. 1. Jäkel S
    2. Dimou L

    (2017) Glial cells and their function in the adult brain: a journey through the history of their ablation

    Frontiers in Cellular Neuroscience 11:24.

    https://doi.org/10.3389/fncel.2017.00024

    • PubMed
    • Google Scholar
38. 1. Jennings CG
    2. Dyer SM
    3. Burden SJ

    (1993) Muscle-specific trk-related receptor with a kringle domain defines a distinct class of receptor tyrosine kinases

    PNAS 90:2895–2899.

    https://doi.org/10.1073/pnas.90.7.2895

    • PubMed
    • Google Scholar
39. 1. Kang H
    2. Tian L
    3. Son YJ
    4. Zuo Y
    5. Procaccino D
    6. Love F
    7. Hayworth C
    8. Trachtenberg J
    9. Mikesh M
    10. Sutton L
    11. Ponomareva O
    12. Mignone J
    13. Enikolopov G
    14. Rimer M
    15. Thompson W

    (2007) Regulation of the intermediate filament protein nestin at rodent neuromuscular junctions by innervation and activity

    Journal of Neuroscience 27:5948–5957.

    https://doi.org/10.1523/JNEUROSCI.0621-07.2007

    • PubMed
    • Google Scholar
40. 1. Katz B
    2. Miledi R

    (1966) Input-output relation of a single synapse

    Nature 212:1242–1245.

    https://doi.org/10.1038/2121242a0

    • PubMed
    • Google Scholar
41. 1. Katz B
    2. Miledi R

    (1967) A study of synaptic transmission in the absence of nerve impulses

    The Journal of Physiology 192:407–436.

    https://doi.org/10.1113/jphysiol.1967.sp008307

    • PubMed
    • Google Scholar
42. 1. Kim D
    2. Paggi JM
    3. Park C
    4. Bennett C
    5. Salzberg SL

    (2019) Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype

    Nature Biotechnology 37:907–915.

    https://doi.org/10.1038/s41587-019-0201-4

    • PubMed
    • Google Scholar
43. 1. Ko CP
    2. Robitaille R

    (2015) Perisynaptic schwann cells at the neuromuscular synapse: adaptable, multitasking glial cells

    Cold Spring Harbor Perspectives in Biology 7:a020503.

    https://doi.org/10.1101/cshperspect.a020503

    • PubMed
    • Google Scholar
44. 1. Koirala S
    2. Qiang H
    3. Ko CP

    (2000) Reciprocal interactions between perisynaptic schwann cells and regenerating nerve terminals at the frog neuromuscular junction

    Journal of Neurobiology 44:343–360.

    https://doi.org/10.1002/1097-4695(20000905)44:3<343::AID-NEU5>3.0.CO;2-O

    • PubMed
    • Google Scholar
45. 1. Kong Y

    (2011) Btrim: a fast, lightweight adapter and quality trimming program for next-generation sequencing technologies

    Genomics 98:152–153.

    https://doi.org/10.1016/j.ygeno.2011.05.009

    • PubMed
    • Google Scholar
46. 1. Lee YI
    2. Thompson WJ
    3. Harlow ML

    (2017) Schwann cells participate in synapse elimination at the developing neuromuscular junction

    Current Opinion in Neurobiology 47:176–181.

    https://doi.org/10.1016/j.conb.2017.10.010

    • PubMed
    • Google Scholar
47. 1. Love MI
    2. Huber W
    3. Anders S

    (2014) Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

    Genome Biology 15:550.

    https://doi.org/10.1186/s13059-014-0550-8

    • PubMed
    • Google Scholar
48. 1. Love FM
    2. Thompson WJ

    (1998) Schwann cells proliferate at rat neuromuscular junctions during development and regeneration

    The Journal of Neuroscience 18:9376–9385.

    https://doi.org/10.1523/JNEUROSCI.18-22-09376.1998

    • PubMed
    • Google Scholar
49. 1. Lwebuga-Mukasa JS
    2. Lappi S
    3. Taylor P

    (1976) Molecular forms of acetylcholinesterase from Torpedo californica: their relationship to synaptic membranes

    Biochemistry 15:1425–1434.

    https://doi.org/10.1021/bi00652a012

    • PubMed
    • Google Scholar
50. 1. Matthias K
    2. Kirchhoff F
    3. Seifert G
    4. Hüttmann K
    5. Matyash M
    6. Kettenmann H
    7. Steinhäuser C

    (2003) Segregated expression of AMPA-type glutamate receptors and glutamate transporters defines distinct astrocyte populations in the mouse Hippocampus

    The Journal of Neuroscience 23:1750–1758.

    https://doi.org/10.1523/JNEUROSCI.23-05-01750.2003

    • PubMed
    • Google Scholar
51. 1. Miledi R
    2. Slater CR

    (1968) Electrophysiology and electron-microscopy of rat neuromuscular junctions after nerve degeneration

    Proc. R. Soc. London. Ser. B. Biol. Sci 169:289–306.

    https://doi.org/10.1098/rspb.1968.0012

    • Google Scholar
52. 1. Miledi R
    2. Slater CR

    (1970) On the degeneration of rat neuromuscular junctions after nerve section

    The Journal of Physiology 207:507–528.

    https://doi.org/10.1113/jphysiol.1970.sp009076

    • PubMed
    • Google Scholar
53. 1. Moloney EB
    2. de Winter F
    3. Verhaagen J

    (2014) ALS as a distal axonopathy: molecular mechanisms affecting neuromuscular junction stability in the presymptomatic stages of the disease

    Frontiers in Neuroscience 8:252.

    https://doi.org/10.3389/fnins.2014.00252

    • PubMed
    • Google Scholar
54. 1. Morris JK
    2. Lin W
    3. Hauser C
    4. Marchuk Y
    5. Getman D
    6. Lee KF

    (1999) Rescue of the cardiac defect in ErbB2 mutant mice reveals essential roles of ErbB2 in peripheral nervous system development

    Neuron 23:273–283.

    https://doi.org/10.1016/S0896-6273(00)80779-5

    • PubMed
    • Google Scholar
55. 1. Moshrefi-Ravasdjani B
    2. Dublin P
    3. Seifert G
    4. Jennissen K
    5. Steinhäuser C
    6. Kafitz KW
    7. Rose CR

    (2017) Changes in the proliferative capacity of NG2 cell subpopulations during postnatal development of the mouse Hippocampus

    Brain Structure and Function 222:831–847.

    https://doi.org/10.1007/s00429-016-1249-2

    • PubMed
    • Google Scholar
56. 1. Mozer BA
    2. Sandstrom DJ

    (2012) Drosophila neuroligin 1 regulates synaptic growth and function in response to activity and phosphoinositide-3-kinase

    Molecular and Cellular Neuroscience 51:89–100.

    https://doi.org/10.1016/j.mcn.2012.08.010

    • PubMed
    • Google Scholar
57. 1. Musarella M
    2. Alcaraz G
    3. Caillol G
    4. Boudier JL
    5. Couraud F
    6. Autillo-Touati A

    (2006) Expression of Nav1.6 sodium channels by Schwann cells at neuromuscular junctions: role in the motor endplate disease phenotype

    Glia 53:13–23.

    https://doi.org/10.1002/glia.20252

    • PubMed
    • Google Scholar
58. 1. Nitkin RM
    2. Smith MA
    3. Magill C
    4. Fallon JR
    5. Yao YM
    6. Wallace BG
    7. McMahan UJ

    (1987) Identification of Agrin, a synaptic organizing protein from Torpedo electric organ

    The Journal of Cell Biology 105:2471–2478.

    https://doi.org/10.1083/jcb.105.6.2471

    • PubMed
    • Google Scholar
59. 1. O'Malley JP
    2. Waran MT
    3. Balice-Gordon RJ

    (1999) In vivo observations of terminal schwann cells at normal, denervated, and reinnervated mouse neuromuscular junctions

    Journal of Neurobiology 38:270–286.

    https://doi.org/10.1002/(SICI)1097-4695(19990205)38:2<270::AID-NEU9>3.0.CO;2-F

    • PubMed
    • Google Scholar
60. 1. Park SY
    2. Jang SY
    3. Shin YK
    4. Jung DK
    5. Yoon BA
    6. Kim JK
    7. Jo YR
    8. Lee HJ
    9. Park HT

    (2017) The scaffolding protein, Grb2-associated Binder-1, in skeletal muscles and terminal schwann cells regulates postnatal neuromuscular synapse maturation

    Experimental Neurobiology 26:141–150.

    https://doi.org/10.5607/en.2017.26.3.141

    • PubMed
    • Google Scholar
61. 1. Peng F
    2. Yao H
    3. Bai X
    4. Zhu X
    5. Reiner BC
    6. Beazely M
    7. Funa K
    8. Xiong H
    9. Buch S

    (2010) Platelet-derived growth factor-mediated induction of the synaptic plasticity gene arc/Arg3.1

    Journal of Biological Chemistry 285:21615–21624.

    https://doi.org/10.1074/jbc.M110.107003

    • PubMed
    • Google Scholar
62. 1. Peper K
    2. Dreyer F
    3. Sandri C
    4. Akert K
    5. Moor H

    (1974) Structure and ultrastructure of the frog motor endplate a freeze-etching study

    Cell and Tissue Research 149:437–455.

    https://doi.org/10.1007/BF00223024

    • PubMed
    • Google Scholar
63. 1. Perez VJ
    2. Moore BW

    (1968) Wallerian degeneration in rabbit tibial nerve: changes in amounts of the S-100 protein

    Journal of Neurochemistry 15:971–977.

    https://doi.org/10.1111/j.1471-4159.1968.tb11640.x

    • PubMed
    • Google Scholar
64. 1. Personius KE
    2. Slusher BS
    3. Udin SB

    (2016) Neuromuscular NMDA receptors modulate developmental synapse elimination

    The Journal of Neuroscience 36:8783–8789.

    https://doi.org/10.1523/JNEUROSCI.1181-16.2016

    • PubMed
    • Google Scholar
65. 1. Petrov KA
    2. Girard E
    3. Nikitashina AD
    4. Colasante C
    5. Bernard V
    6. Nurullin L
    7. Leroy J
    8. Samigullin D
    9. Colak O
    10. Nikolsky E
    11. Plaud B
    12. Krejci E

    (2014) Schwann cells sense and control acetylcholine spillover at the neuromuscular junction by α7 nicotinic receptors and butyrylcholinesterase

    Journal of Neuroscience 34:11870–11883.

    https://doi.org/10.1523/JNEUROSCI.0329-14.2014

    • PubMed
    • Google Scholar
66. 1. Pinard A
    2. Lévesque S
    3. Vallée J
    4. Robitaille R

    (2003) Glutamatergic modulation of synaptic plasticity at a PNS vertebrate cholinergic synapse

    European Journal of Neuroscience 18:3241–3250.

    https://doi.org/10.1111/j.1460-9568.2003.03028.x

    • PubMed
    • Google Scholar
67. 1. Platel JC
    2. Gordon V
    3. Heintz T
    4. Bordey A

    (2009) GFAP-GFP neural progenitors are antigenically homogeneous and anchored in their enclosed mosaic niche

    Glia 57:66–78.

    https://doi.org/10.1002/glia.20735

    • PubMed
    • Google Scholar
68. 1. Porter S
    2. Froehner SC

    (1983)

    Characterization and localization of the mr = 43,000 proteins associated with acetylcholine receptor-rich membranes

    The Journal of Biological Chemistry 258:10034–10040.

    • PubMed
    • Google Scholar
69. 1. Rafuse VF
    2. Polo-Parada L
    3. Landmesser LT

    (2000) Structural and functional alterations of neuromuscular junctions in NCAM-deficient mice

    The Journal of Neuroscience 20:6529–6539.

    https://doi.org/10.1523/JNEUROSCI.20-17-06529.2000

    • PubMed
    • Google Scholar
70. 1. Ranaivoson FM
    2. Turk LS
    3. Ozgul S
    4. Kakehi S
    5. von Daake S
    6. Lopez N
    7. Trobiani L
    8. De Jaco A
    9. Denissova N
    10. Demeler B
    11. Özkan E
    12. Montelione GT
    13. Comoletti D

    (2019) A proteomic screen of neuronal Cell-Surface molecules reveals IgLONs as structurally conserved interaction modules at the synapse

    Structure 27:893–906.

    https://doi.org/10.1016/j.str.2019.03.004

    • PubMed
    • Google Scholar
71. 1. Reddy LV
    2. Koirala S
    3. Sugiura Y
    4. Herrera AA
    5. Ko CP

    (2003) Glial cells maintain synaptic structure and function and promote development of the neuromuscular junction in vivo

    Neuron 40:563–580.

    https://doi.org/10.1016/S0896-6273(03)00682-2

    • PubMed
    • Google Scholar
72. 1. Reese BE
    2. Keeley PW

    (2015) Design principles and developmental mechanisms underlying retinal mosaics

    Biological Reviews 90:854–876.

    https://doi.org/10.1111/brv.12139

    • PubMed
    • Google Scholar
73. 1. Reist NE
    2. Smith SJ

    (1992) Neurally evoked calcium transients in terminal schwann cells at the neuromuscular junction

    PNAS 89:7625–7629.

    https://doi.org/10.1073/pnas.89.16.7625

    • PubMed
    • Google Scholar
74. 1. Reynolds ML
    2. Woolf CJ

    (1992) Terminal schwann cells elaborate extensive processes following denervation of the motor endplate

    Journal of Neurocytology 21:50–66.

    https://doi.org/10.1007/BF01206897

    • PubMed
    • Google Scholar
75. 1. Riethmacher D
    2. Sonnenberg-Riethmacher E
    3. Brinkmann V
    4. Yamaai T
    5. Lewin GR
    6. Birchmeier C

    (1997) Severe neuropathies in mice with targeted mutations in the ErbB3 receptor

    Nature 389:725–730.

    https://doi.org/10.1038/39593

    • PubMed
    • Google Scholar
76. 1. Robertson JD

    (1956) The ultrastructure of a reptilian myoneural junction

    The Journal of Biophysical and Biochemical Cytology 2:381–394.

    https://doi.org/10.1083/jcb.2.4.381

    • PubMed
    • Google Scholar
77. 1. Robitaille R

    (1995) Purinergic receptors and their activation by endogenous purines at Perisynaptic glial cells of the frog neuromuscular junction

    The Journal of Neuroscience 15:7121–7131.

    https://doi.org/10.1523/JNEUROSCI.15-11-07121.1995

    • PubMed
    • Google Scholar
78. 1. Robitaille R
    2. Bourque MJ
    3. Vandaele S

    (1996) Localization of L-type Ca2+ channels at Perisynaptic glial cells of the frog neuromuscular junction

    The Journal of Neuroscience 16:148–158.

    https://doi.org/10.1523/JNEUROSCI.16-01-00148.1996

    • PubMed
    • Google Scholar
79. 1. Robitaille R
    2. Jahromi BS
    3. Charlton MP

    (1997) Muscarinic Ca2+ responses resistant to muscarinic antagonists at Perisynaptic schwann cells of the frog neuromuscular junction

    The Journal of Physiology 504:337–347.

    https://doi.org/10.1111/j.1469-7793.1997.337be.x

    • PubMed
    • Google Scholar
80. 1. Rochon D
    2. Rousse I
    3. Robitaille R

    (2001) Synapse-glia interactions at the mammalian neuromuscular junction

    The Journal of Neuroscience 21:3819–3829.

    https://doi.org/10.1523/JNEUROSCI.21-11-03819.2001

    • PubMed
    • Google Scholar
81. 1. Sanes JR
    2. Lichtman JW

    (1999) Development of the vertebrate neuromuscular junction

    Annual Review of Neuroscience 22:389–442.

    https://doi.org/10.1146/annurev.neuro.22.1.389

    • PubMed
    • Google Scholar
82. 1. Sanes JR
    2. Lichtman JW

    (2001) Induction, assembly, maturation and maintenance of a postsynaptic apparatus

    Nature Reviews Neuroscience 2:791–805.

    https://doi.org/10.1038/35097557

    • PubMed
    • Google Scholar
83. 1. Sealock R
    2. Murnane AA
    3. Paulin D
    4. Froehner SC

    (1989) Immunochemical identification of desmin in Torpedo postsynaptic membranes and at the rat neuromuscular junction

    Synapse 3:315–324.

    https://doi.org/10.1002/syn.890030404

    • PubMed
    • Google Scholar
84. 1. Shapiro L
    2. Love J
    3. Colman DR

    (2007) Adhesion molecules in the nervous system: structural insights into function and diversity

    Annual Review of Neuroscience 30:451–474.

    https://doi.org/10.1146/annurev.neuro.29.051605.113034

    • PubMed
    • Google Scholar
85. 1. Smith IW
    2. Mikesh M
    3. Lee Y
    4. Thompson WJ

    (2013) Terminal schwann cells participate in the competition underlying neuromuscular synapse elimination

    Journal of Neuroscience 33:17724–17736.

    https://doi.org/10.1523/JNEUROSCI.3339-13.2013

    • PubMed
    • Google Scholar
86. 1. Sobel A
    2. Weber M
    3. Changeux JP

    (1977) Large-scale purification of the acetylcholine-receptor protein in its membrane-bound and detergent-extracted forms from Torpedo marmorata electric organ

    European Journal of Biochemistry 80:215–224.

    https://doi.org/10.1111/j.1432-1033.1977.tb11874.x

    • PubMed
    • Google Scholar
87. 1. Sobel A
    2. Hofler J
    3. Heidmann T
    4. Changeux JP

    (1979)

    Structural and functional properties of the acetylcholine regulator

    Advances in Cytopharmacology 3:191–196.

    • PubMed
    • Google Scholar
88. 1. Son YJ
    2. Thompson WJ

    (1995) Schwann cell processes guide regeneration of peripheral axons

    Neuron 14:125–132.

    https://doi.org/10.1016/0896-6273(95)90246-5

    • PubMed
    • Google Scholar
89. 1. Stallcup WB

    (1981) The NG2 antigen, a putative lineage marker: immunofluorescent localization in primary cultures of rat brain

    Developmental Biology 83:154–165.

    https://doi.org/10.1016/S0012-1606(81)80018-8

    • PubMed
    • Google Scholar
90. 1. Trachtenberg JT
    2. Thompson WJ

    (1996) Schwann cell apoptosis at developing neuromuscular junctions is regulated by glial growth factor

    Nature 379:174–177.

    https://doi.org/10.1038/379174a0

    • PubMed
    • Google Scholar
91. 1. Trachtenberg JT
    2. Thompson WJ

    (1997) Nerve terminal withdrawal from rat neuromuscular junctions induced by neuregulin and schwann cells

    The Journal of Neuroscience 17:6243–6255.

    https://doi.org/10.1523/JNEUROSCI.17-16-06243.1997

    • PubMed
    • Google Scholar
92. 1. Vives V
    2. Alonso G
    3. Solal AC
    4. Joubert D
    5. Legraverend C

    (2003) Visualization of S100B-positive neurons and Glia in the central nervous system of EGFP transgenic mice

    The Journal of Comparative Neurology 457:404–419.

    https://doi.org/10.1002/cne.10552

    • PubMed
    • Google Scholar
93. 1. Wassle H
    2. Riemann HJ

    (1978) The mosaic of Nhtman,erve cells in the mammalian retina

    Proc. R. Soc. London - Biol. Sci 200:441–461.

    https://doi.org/10.1098/rspb.1978.0026

    • Google Scholar
94. 1. Woldeyesus MT
    2. Britsch S
    3. Riethmacher D
    4. Xu L
    5. Sonnenberg-Riethmacher E
    6. Abou-Rebyeh F
    7. Harvey R
    8. Caroni P
    9. Birchmeier C

    (1999) Peripheral nervous system defects in erbB2 mutants following genetic rescue of heart development

    Genes & Development 13:2538–2548.

    https://doi.org/10.1101/gad.13.19.2538

    • PubMed
    • Google Scholar
95. 1. Wright MC
    2. Potluri S
    3. Wang X
    4. Dentcheva E
    5. Gautam D
    6. Tessler A
    7. Wess J
    8. Rich MM
    9. Son YJ

    (2009) Distinct muscarinic acetylcholine receptor subtypes contribute to stability and growth, but not compensatory plasticity, of neuromuscular synapses

    Journal of Neuroscience 29:14942–14955.

    https://doi.org/10.1523/JNEUROSCI.2276-09.2009

    • PubMed
    • Google Scholar
96. 1. Yang JF
    2. Cao G
    3. Koirala S
    4. Reddy LV
    5. Ko CP

    (2001) Schwann cells express active agrin and enhance aggregation of acetylcholine receptors on muscle fibers

    The Journal of Neuroscience 21:9572–9584.

    https://doi.org/10.1523/JNEUROSCI.21-24-09572.2001

    • PubMed
    • Google Scholar
97. 1. Young P
    2. Nie J
    3. Wang X
    4. McGlade CJ
    5. Rich MM
    6. Feng G

    (2005) LNX1 is a perisynaptic schwann cell specific E3 ubiquitin ligase that interacts with ErbB2

    Molecular and Cellular Neuroscience 30:238–248.

    https://doi.org/10.1016/j.mcn.2005.07.015

    • PubMed
    • Google Scholar
98. 1. Zhu X
    2. Bergles DE
    3. Nishiyama A

    (2008) NG2 cells generate both oligodendrocytes and gray matter astrocytes

    Development 135:145–157.

    https://doi.org/10.1242/dev.004895

    • PubMed
    • Google Scholar
99. 1. Zuo Y
    2. Lubischer JL
    3. Kang H
    4. Tian L
    5. Mikesh M
    6. Marks A
    7. Scofield VL
    8. Maika S
    9. Newman C
    10. Krieg P
    11. Thompson WJ

    (2004) Fluorescent proteins expressed in mouse transgenic lines mark subsets of Glia, neurons, macrophages, and dendritic cells for vital examination

    Journal of Neuroscience 24:10999–11009.

    https://doi.org/10.1523/JNEUROSCI.3934-04.2004

    • PubMed
    • Google Scholar

Author details

1. Ryan Castro

   1. Department of Molecular Biology, Cellular Biology, and Biochemistry, Brown University, Providence, United States
   2. Neuroscience Graduate Program, Brown University, Providence, United States

   Contribution

   Formal analysis, Investigation, Methodology, Writing - original draft, Writing - review and editing

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0002-2316-8039

2. Thomas Taetzsch

   Department of Molecular Biology, Cellular Biology, and Biochemistry, Brown University, Providence, United States

   Contribution

   Formal analysis, Investigation, Methodology, Writing - original draft, Writing - review and editing

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0003-3257-1142

3. Sydney K Vaughan

   Department of Molecular Biology, Cellular Biology, and Biochemistry, Brown University, Providence, United States

   Contribution

   Data curation, Formal analysis, Writing - original draft, Writing - review and editing

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0002-3427-4654

4. Kerilyn Godbe

   Fralin Biomedical Research Institute at Virginia Tech Carilion, Roanoke, United States

   Contribution

   Formal analysis, Writing - review and editing

   Competing interests

   No competing interests declared

5. John Chappell

   Fralin Biomedical Research Institute at Virginia Tech Carilion, Roanoke, United States

   Contribution

   Resources, Writing - review and editing

   Competing interests

   No competing interests declared

6. Robert E Settlage

   Department of Advanced Research Computing, Virginia Tech, Blacksburg, United States

   Contribution

   Formal analysis, Methodology, Writing - original draft, Writing - review and editing

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0002-1354-7609

7. Gregorio Valdez

   Department of Molecular Biology, Cellular Biology, and Biochemistry, Brown University, Providence, United States

   Contribution

   Conceptualization, Resources, Data curation, Formal analysis, Supervision, Funding acquisition, Investigation, Methodology, Writing - original draft, Writing - review and editing

   For correspondence

   gregorio_valdez@brown.edu

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0002-0375-4532

• 3,886

  views

• 434

  downloads

• 52

  citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.