2004). These cells also express nestin, which is not expressed by stellate astrocytes but is found on the majority of neuronal progenitor cells in the adult brain (Mignone et al. 2004). After rodent SCI, injected radial glia can be neuroprotective and improve functional recovery (Hasegawa et al. 2005; Chang et al. 2009). Studies in optic nerve regeneration in young rats suggested that not only neonatal astrocytes but Inhibitors,research,lifescience,medical also astrocyte-like glia in older rats improve and support axonal regeneration (Dyson et al. 1988; Harvey and Tan 1992); however, the cellular process that guides this regeneration remains unclear. In addition,
neuronal stem cells expressing transcription factor, such as Sox2, are also Tubacin increased after SCI (Lee et al. 2012; Rodriguez-Jimnez et al. 2012). With the right factors, local and reactive astrocytes in the gray and white matter Inhibitors,research,lifescience,medical may be turned into radial glia or neuronal progenitors that better support neurogenesis and regeneration. The application of fibroblast growth factor (Fgf)2 has been shown to promote functional recovery after brain injury (Dietrich et al. 1996; McDermott et al.
1997), stroke (Kawamata et al. 1996, 1997), or SCI (Lee et al. 1999; Rabchevsky et al. 1999; Yan et al. 2000). Inhibitors,research,lifescience,medical In Inhibitors,research,lifescience,medical SCI the recovery is thought to be due to Fgf promoting neuronal survival (Teng et al. 1998, 1999), angiogenesis (Kang et al. 2013), and causing a reduction in injury volume (Lee et al. 1999; Rabchevsky et al. 1999). Several therapies that claim regenerative effects after transplanting specific cells also contain a cocktail of factors including Fgf1 and Fgf2 (Meijs et al. 2004; Kuo et al. 2011; Guzen et al. 2012; Lu et al. 2012), and thus, the proregenerative capacity attributed to transplanted cells
may in fact partially Inhibitors,research,lifescience,medical be due to the proregenerative effects of Fgf signaling. Furthermore, Fgf are currently in clinical trials in human patients with cervical SCI (Wu et al. 2008). Therefore, it is important to understand the cellular and molecular mechanism by which Fgf contributes to regeneration. We recently demonstrated that Fgf signaling plays a crucial Entinostat role in glial cell differentiation and morphogenesis that is required for regeneration after SCI in zebrafish (Goldshmit et al. 2012). After SCI in adult zebrafish, radial glia in the central canal form bridges to support axonal regeneration through the lesion. Moreover, we and others have demonstrated that in zebrafish radial glia at the injury site generate new neurons during regeneration (Reimer et al. 2008; Hui et al. 2010; Kroehne et al. 2011).