SOD1G93A mice were crossed with S100-GFP;NG2-dsRed mice to generate S100-GFP;NG2-dsRed;SOD1G93A mice. in synapse development, function, maintenance, and repair. The study of PSCs has relied on an anatomy-based approach, as the identities of cell-specific PSC molecular markers have remained elusive. This limited approach has precluded our ability to isolate and genetically manipulate PSCs in a cell specific manner. We have identified neuron-glia antigen 2 (NG2) as a unique molecular marker of S100+ PSCs in skeletal muscle. NG2 is usually expressed in Schwann cells already associated with the NMJ, indicating that it is a marker of differentiated PSCs. Using a newly generated transgenic mouse in which PSCs are specifically labeled, we show that PSCs have a unique molecular signature that includes genes known to play critical roles in PSCs and synapses. These findings will serve as a springboard for revealing drivers of PSC differentiation and function. Research organism: Mouse Introduction The neuromuscular junction (NMJ) is usually a tripartite synapse comprised of an -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 Rabbit Polyclonal to SH3GLB2 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 Closantel 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 Closantel Thompson, 2008; Boeke, 1949; Heuser and Reese, 1973; Miledi and Slater, 1968; Miledi and Slater, 1970; Peper et al., 1974; Astrow et Closantel 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 Closantel 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, Closantel 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.