Distinct roles of neuroepithelial-like and radial glia-like progenitor cells in cerebellar regeneration

Abstract

Zebrafish can regenerate after brain injury, and the regenerative process is driven by resident stem cells. Stem cells are heterogeneous in the vertebrate brain, but the significance of having heterogeneous stem cells in regeneration is not understood. Limited availability of specific stem cells might impair the regeneration of particular cell lineages. We studied regeneration of the adult zebrafish cerebellum, which contains two major stem and progenitor cell types: ventricular zone and neuroepithelial cells. Using conditional lineage tracing we demonstrate that cerebellar regeneration depends on the availability of specific stem cells. Radial glia-like cells are thought to be the predominant stem cell type in homeostasis and after injury. However, we find that radial glia-like cells play a minor role in adult cerebellar neurogenesis and in recovery after injury. Instead, we find that neuroepithelial cells are the predominant stem cell type supporting cerebellar regeneration after injury. Zebrafish are able to regenerate many, but not all, cell types in the cerebellum, which emphasizes the need to understand the contribution of different adult neural stem and progenitor cell subtypes in the vertebrate central nervous system.

Wnt signaling regulates proliferation and differentiation of radial glia in regenerative processes after stab injury in the optic tectum of adult zebrafish

“…However, RG in the telencephalon, hypothalamus and spinal cord of adult zebrafish function as neural stem cells in both adult and regenerative neurogenesis (Adolf et al, ; Gorsuch et al, ; Hui, Nag, and Ghosh, ; Johnson et al, ; Kishimoto et al, ; Kizil et al, 2012; Kroehne, Freudenreich, Hans, Kaslin, and Brand, ; Mokalled et al, ; Raymond et al, ). Moreover, in the cerebellum, NE, but not RG, operate as neural stem cells in both physiological and regenerative conditions (Bae et al, ; Kaslin, Kroehne, Ganz, Hans, & Brand, ). RG and NE have different capacities as neural stem cell in different regions of the CNS and it is not well known how the regenerative abilities of RG and NE as neural stem cells are regulated.…”

“…In the adult telencephalon, radial glia (RG) operate as neural stem cells in both physiological and regenerative conditions and Notch and FGF signaling have been reported to control the ability of RG to generate new neurons in both conditions (Ganz, Kaslin, Hochmann, Freudenreich, & Brand, ; Kishimoto, Shimizu, & Sawamoto, ). However, few studies have examined other parts of the brain, such as the olfactory bulb, optic tectum, and cerebellum (Galant et al, ; Kaslin et al, ).…”

Involvement of sonic hedgehog and notch signaling in regenerative neurogenesis in adult zebrafish optic tectum after stab injury

“…During neuronal regeneration in telencephalon, it was shown that radial glia (RG) function as neural stem cells (Baumgart, Barbosa, Bally‐Cuif, Götz, & Ninkovic, ; Diotel et al, ; Kroehne et al, ; Kyritsis et al, ). Recently, neuronal regeneration has also been reported to occur in the cerebellum (Kaslin, Kroehne, Ganz, Hans, & Brand, ; Zupanc, Hinsch, & Gage, ). However, in cerebellar regeneration, primarily neuroepithelial‐like stem cells (NE), rather than the RG, serve as neural stem cells after stab injury (Kaslin et al, ).…”

“…Recently, neuronal regeneration has also been reported to occur in the cerebellum (Kaslin, Kroehne, Ganz, Hans, & Brand, ; Zupanc, Hinsch, & Gage, ). However, in cerebellar regeneration, primarily neuroepithelial‐like stem cells (NE), rather than the RG, serve as neural stem cells after stab injury (Kaslin et al, ). Thus, RG may have region‐specific roles throughout the CNS.…”

“…cells (NE), rather than the RG, serve as neural stem cells after stab injury (Kaslin et al, 2017). Thus, RG may have region-specific roles throughout the CNS.…”