PUBLICATION

Wnt/β-catenin signaling was activated in supporting cells during exposure of the zebrafish lateral line to cisplatin

Authors
Mi, X.X., Yan, J., Li, Y., Shi, J.P.
ID
ZDB-PUB-190724-28
Date
2019
Source
Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft   226: 48-56 (Journal)
Registered Authors
Keywords
Hair cell regeneration, Regeneration capacity, Supporting cells, Wnt/β-catenin, Zebrafish lateral line
MeSH Terms
  • Animals
  • Antineoplastic Agents/toxicity*
  • Cell Death/drug effects
  • Cisplatin/toxicity*
  • Gene Expression/drug effects
  • Lateral Line System/cytology*
  • Lateral Line System/drug effects*
  • Nerve Regeneration/drug effects
  • Neurons/drug effects
  • Stem Cells/drug effects
  • Wnt Signaling Pathway/drug effects*
  • Wnt Signaling Pathway/genetics
  • Zebrafish
  • beta Catenin/drug effects
  • beta Catenin/genetics
PubMed
31330310 Full text @ Ann. Anat.
Abstract
Zebrafish lateral line neuromasts are composed of central hair cells surrounded by supporting cells. Cisplatin is a common anticancer drug, with hair cell disruption being a frequent side effect of this drug. In our study, we observed complete functional hair cell loss after six hours of cisplatin insult in neuromasts, as demonstrated by anti-parvalbumin 3 immunofluorescence staining or YO-PRO1 vital dye staining. Time course analysis of neuromast hair cell regeneration showed that regenerated hair cells first appeared between 12 and 24hours after damage, and the abundance of these cells increased stepwise with recovery time. After 72hours, 90% of the hair cells were regenerated, and after 84hours, the number of regenerated hair cells was comparable to the number of neuromast hair cells before treatment. The expression pattern of slc17a8 also showed that hair cells were regenerated after cisplatin exposure. Meanwhile, peripheral supporting cells moved toward the center of the neuromasts, as shown by the in situ expression pattern of sox21a. Increased hair cell progenitor formation was also observed, as demonstrated by the in situ expression pattern of atoh1a. Furthermore, we detected increased expression of wnt2, wnt3a, and ctnnb1 in sorted supporting cells from the sqet10 transgenic line,which labels neuromast supporting cells specifically. In situ hybridization analysis also showed decreased expression of dkk1a and dkk2. Regenerated hair cells were inhibited by early inhibition of Wnt/β-catenin signaling. Taken together, the results presented here showed that Wnt/β-catenin signaling was activated in supporting cells during cisplatin exposure earlier than expected. Our results also indicated that supporting cells enabled hair cell regeneration via Wnt/β-catenin signaling during cisplatin exposure.
Errata / Notes
This article is corrected by ZDB-PUB-211101-2.
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
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Orthology
Engineered Foreign Genes
Mapping