Radial glial progenitors repair the zebrafish spinal cord following transection

Abstract

In mammals, spinal cord injury results in permanent sensory-motor loss due in part to a failure in reinitiating local neurogenesis. However, zebrafish show robust neuronal regeneration and functional recovery even after complete spinal cord transection. Postembryonic neurogenesis is dependent upon resident multipotent progenitors, which have been identified in multiple vertebrates. One candidate cell population for injury repair expresses Dbx1, which has been shown to label multipotent progenitors in mammals. In this study, we use specific markers to show that cells expressing a dbx1a:GFP reporter in the zebrafish spinal cord are radial glial progenitors that continue to generate neurons after embryogenesis. We also use a novel larval spinal cord transection assay to show that dbx1a:GFP+ cells exhibit a proliferative and neurogenic response to injury, and contribute newly-born neurons to the regenerative blastema. Together, our data indicate that dbx1a:GFP+ radial glia may be stem cells for the regeneration of interneurons following spinal cord injury in zebrafish.

Hypothalamic radial glia function as self-renewing neural progenitors in the absence of Wnt/ß-catenin signaling

“…1D). A consistent minority of cells labeled by her4.3:EGFP were also GS − , potentially representing non-glial progeny due to GFP perdurance (Briona and Dorsky, 2014). By contrast, we did not observe expression of either Gfap or S100β (data not shown) in this region.…”

Wnt/ß-catenin signaling is required for radial glial neurogenesis following spinal cord injury

“…Larvae were lesioned at 5dpf as described previously (Briona and Dorsky, 2014a, b). Briefly, microinjection pipettes were broken, beveled and used as glass scalpels.…”

“…Larvae intended for cryosectioning before immunohistochemistry were fixed in fresh 4% PFA for 1 hour at room temperature, and washed and cryosectioned as described previously (Briona and Dorsky, 2014a). Larvae intended for whole mount immunohistochemistry were fixed overnight in fresh 4% PFA at 4°C, equilibrated in PTW, heat treated in 70°C Tris-HCl pH 9.0 and dehydrated with acetone as described previously (Inoue and Wittbrodt, 2011).…”

“…Ascending and descending axons can regrow from surviving neurons far from the injury (Becker et al, 1997), but restoration of motoneuron and interneuron populations after injury relies upon local neural progenitor cells (Briona and Dorsky, 2014a; Hui et al, 2010; Reimer et al, 2008). In zebrafish, neural progenitors persist beyond embryogenesis throughout the CNS as a subpopulation of radial glia (Kroehne et al, 2011; Rothenaigner et al, 2011).…”

Neuronal Regeneration from Ependymo-Radial Glial Cells: Cook, Little Pot, Cook!

“…Just dorsal to the pMN-like domain, so-called V2 interneurons, expressing the marker vsx1, and ventral to the pMNlike domain, serotonergic neurons appear to emerge from the ERG cell layer (Figure 3) (Kuscha et al, 2012a(Kuscha et al, , 2012bReimer et al, 2008). In the post-embryonic zebrafish spinal cord, medial dbx1-expressing ERGs also exhibit a neurogenic response to injury (Briona and Dorsky, 2014). This suggests that different post-embryonic and adult progenitor cells in the spinal cord regenerate different types of neurons, dictated by the developmental origin of the ERGs.…”