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.
The authors declare no competing or financial interests.
J.K. and M.B. conceptualised, designed and provided resources for the work. J.K. performed experiments, analysed data and wrote the manuscript. J.G., V.K. and S.H. co-performed experiments and commented on the manuscript.
This work was supported by grants from the Deutsche Forschungsgemeinschaft (SFB 655-A3), European Union (European Research Council AdG Zf-BrainReg) and the German Excellence Initiative of the Bundesministerium für Bildung und Forschung (Institutional Strategy, TU Dresden) to M.B., and Erdi Foundation and National Health and Medical Research Council project grant (GNT1060538), Faculty of Medicine, Nursing and Health Sciences, Monash University strategic grant to J.K. The Australian Regenerative Medicine Institute is supported by funds from the state government of Victoria and the Australian federal government.
Supplementary information available online at http://dev.biologists.org/lookup/doi/10.1242/dev.144907.supplemental
- Received September 20, 2016.
- Accepted March 3, 2017.