Ionizing Radiation Blocks Hair Cell Regeneration in Zebrafish Lateral Line Neuromasts by Preventing Wnt Signaling

Li, R., Liao, G., Yin, G., Wang, B., Yan, M., Lin, X., Zhang, W., Chen, X., Du, S., Yuan, Y.
Molecular neurobiology   55(2): 1639-1651 (Journal)
Registered Authors
Chen, Xiaohui, Zhang, Wenqing
Neuromast, Radiotherapy, Regeneration, Supporting cell, Zebrafish
MeSH Terms
  • Animals
  • Cell Proliferation/radiation effects*
  • Hair Cells, Auditory/metabolism
  • Hair Cells, Auditory/radiation effects*
  • Lateral Line System/cytology
  • Lateral Line System/metabolism
  • Lateral Line System/radiation effects*
  • Radiation, Ionizing*
  • Regeneration/radiation effects
  • Wnt Signaling Pathway/radiation effects*
  • Zebrafish
28194644 Full text @ Mol. Neurobiol.
Loss of hair cells occurs after radiotherapy, which is a major treatment modality for head and neck cancers. In the lateral line neuromasts of zebrafish, hair cells regenerate rapidly from supporting cells after damage from ototoxins. To investigate hair cell regeneration after radiation damage, zebrafish larvae were exposed to radiation, and hair cells were counted and cell proliferation was detected in neuromasts. After irradiation exposure, cell proliferation was inhibited in neuromasts and the number of supporting cells remained stable. There was a gradual loss of hair cells in lateral line neuromasts, which was not followed by regeneration. An activator of Wnt signaling (1-azakenpaullone) promoted robust regeneration of hair cells in irradiated neuromasts. By the quantitative real-time PCR and immunofluorescence, dkk2, an inhibitory Wnt ligand, was identified upregulated in irradiated neuromasts. Accelerating the death process of irradiated hair cells by treatment with neomycin also restored the regenerative capacity of neuromasts. However, a proportion of the new hair cells died within several days after forced regeneration and baseline activity of proliferation in supporting cells remained unimproved. In conclusion, these findings suggested that radiation suppressed hair cell regeneration in zebrafish lateral line neuromasts through inhibition of Wnt signaling in supporting cells possibly by secreting anti-proliferation factors like dkk2. Maintaining a healthy supporting cell pool is vital for regeneration of hair cells.
Genes / Markers
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Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes