RRC ID 54986
Author Shimizu Y, Ueda Y, Ohshima T.
Title Wnt signaling regulates proliferation and differentiation of radial glia in regenerative processes after stab injury in the optic tectum of adult zebrafish.
Journal Glia
Abstract Zebrafish have superior abilities to generate new neurons in the adult brain and to regenerate brain tissue after brain injury compared with mammals. There exist two types of neural stem cells (NSCs): neuroepithelial-like stem cells (NE) and radial glia (RG) in the optic tectum. We established an optic tectum stab injury model to analyze the function of NSCs in the regenerative condition and confirmed that the injury induced the proliferation of RG, but not NE and that the proliferated RG differentiated into new neurons after the injury. We then analyzed the involvement of Wnt signaling after the injury, using a Wnt reporter line in which canonical Wnt signaling activation induced GFP expression and confirmed that GFP expression was induced specifically in RG after the injury. We also analyzed the expression level of genes related to Wnt signaling, and confirmed that endogenous Wnt antagonist dkk1b expression was significantly decreased after the injury. We observed that Wnt signal inhibitor IWR1 treatment suppressed the proliferation and differentiation of RG after the injury, suggesting that up-regulation of Wnt signaling in RG after the stab injury was required for optic tectum regeneration. We also confirmed that Wnt activation by treatment with GSK3β inhibitor BIO in uninjured zebrafish induced proliferation of RG in the optic tectum. This optic tectum stab injury model is useful for the study of the molecular mechanisms of brain regeneration and analysis of the RG functions in physiological and regenerative conditions.
Volume 66(7)
Pages 1382-1394
Published 2018-7-1
DOI 10.1002/glia.23311
PMID 29411422
MeSH Animals Animals, Genetically Modified Cell Differentiation / physiology Cell Proliferation / physiology Ependymoglial Cells / pathology Ependymoglial Cells / physiology* Glycogen Synthase Kinase 3 beta / antagonists & inhibitors Glycogen Synthase Kinase 3 beta / metabolism Green Fluorescent Proteins / genetics Green Fluorescent Proteins / metabolism Intercellular Signaling Peptides and Proteins / metabolism Nerve Regeneration / physiology* Neurons / pathology Neurons / physiology Superior Colliculi / injuries* Superior Colliculi / pathology Superior Colliculi / physiopathology* Wnt Signaling Pathway / physiology* Wounds, Stab / pathology Wounds, Stab / physiopathology* Zebrafish Zebrafish Proteins / metabolism
IF 5.829
Times Cited 12
Zebrafish Tg(6xTcf/LefBS-miniP:d2EGFP) RIKEN WT