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

Zebrafish can regenerate 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 ability of the adult zebrafish cerebellum. The zebrafish cerebellum contains two major stem and progenitor cell types, ventricular zone and neuroepithelial cells. Using conditional lineage tracing, we demonstrate that cerebellar regeneration depends on availability of specific stem cells. Radial glia-like cells are thought to be the predominating stem cell type in homeostasis and after injury. However, we find that radial glia-like cells play a minor part 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 CNS.