Neural stem/progenitor cells are activated during tail regeneration in the leopard gecko (Eublepharis macularius)

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Spinal cord injuries can lead to devastating functional and behavioural impairments including paresis, paralysis and in severe cases, death (Thuret, Moon, & Gage, 2006). In mammals, the regenerative capacity of the central nervous system (CNS) is limited and most spinal cord injuries are resolved with the formation of a glial scar (Horner & Gage, 2000; McDonald & Sadowsky, 2002; Tanaka & Ferretti, 2009). Whereas glial scars are neuroprotective (against severe inflammation) they also inhibit axon regrowth (Frisén et al., 1995; Liu et al., 1997; Rowland, Hawryluk, Kwon, & Fehlings, 2008). Despite numerous efforts to reduce the negative impact of the glial scar, improvements to functional recovery remain limited (Sekiya et al., 2015; Shen, Wang, & Gu, 2014; Zhao & Fawcett, 2013).
One of the main strategies to improve our understanding of spinal cord repair involves the adoption of a comparative approach using regeneration competent models (Tanaka & Reddien, 2011). Across species capable of spinal cord regeneration, the degree to which structure and function of the cord is re‐established varies. Consistently though, spinal cord injuries trigger the proliferation of a stem cell‐like population of cells that is mobilized to replace missing tissue (Bellairs & Bryant, 1985; Benraiss, Arsanto, & Coulon, 1999; Monaghan et al., 2007) The best‐known examples of species capable of spinal cord regeneration following injury include some species of teleost fish (Anderson, Choy, & Waxman, 1986; Hui, Dutta, & Ghosh, 2010), anuran tadpoles (Gaete et al., 2012), and urodele amphibians (Dawley, O Samson, Woodard, & Matthias, 2012; Mchedlishvili, Epperlein, & Telzerow, 2007). Ultimately, these species restore damaged or lost tissue with a replacement that closely resembles the original organ in both structure and function. Among amniotes, only lizards appear to be capable of spontaneous spinal cord regeneration, and only within the tail (Alibardi & Miolo, 1990; McLean & Vickaryous, 2011; Szarek et al., 2016; Whimster, 1978). In stark contrast with non‐amniotes, the regenerated spinal cord of lizards—while functional—is morphologically distinct from that of the original. More specifically, while the original spinal cord consists of white matter, gray matter, and a tubular organization or ependymal layer surrounding the central canal, the regenerate spinal cord includes only descending tracts and an ependymal layer (Egar, Simpson, & Singer, 1970; Gilbert, Delorme, & Vickaryous, 2015; McLean & Vickaryous, 2011; Simpson, 1968). As a result, lizards provide a unique opportunity to investigate functional tissue replacement in the absence of structural replication.
Mounting evidence points toward ependymal layer cells (ELCs) as playing a crucial role during spinal cord regeneration (C. G. Becker & Becker, 2015; Gaete et al., 2012; Tanaka & Ferretti, 2009) In addition to circulating cerebrospinal fluid, it is now understood that the ependymal population includes resident neural stem/progenitor cells (NSPCs). In regeneration‐competent taxa, NSPCs are recruited in response to injury to replace lost or damaged neurons (Allen & Smith, 2012; Reimer et al., 2008; Tanaka & Ferretti, 2009). In zebrafish, ELCs with stem/progenitor‐like properties are retained into adulthood. Although various terms have been used to describe these cells (e.g., ependymo‐radial glia (C. G. Becker & Becker, 2008) or ependymoglia (Kálmán & Ajtai, 2000), we have adopted the term radial glia (Alvarez‐Buylla, García‐Verdugo, & Tramontin, 2001; Stevenson & Yoon, 1982; Zamora & Mutin, 1988). Characteristically, these cells have a radial cell‐like morphology (i.e., the cell body contributes to the lining of the central canal, while a lengthy radial process contacts the pial surface) and express markers otherwise characteristic of astrocytes, such as glial fibrillary acidic protein (GFAP) (C. G. Becker & Becker, 2015) and Vimentin (Zamora & Mutin, 1988). Following injury, radial glia participates in replacing domain‐specific cell types.
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