ZFIN ID: ZDB-PUB-150527-6
LSD1 is Required for Hair Cell Regeneration in Zebrafish
He, Y., Tang, D., Cai, C., Chai, R., Li, H.
Date: 2016
Source: Molecular neurobiology 53(4): 2421-34 (Journal)
Registered Authors:
Keywords: LSD1, Zebrafish, Hair cell, Regeneration, Fgf signaling pathway, Wnt signaling pathway
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Biomarkers/metabolism
  • Cell Count
  • Cell Cycle Checkpoints/drug effects
  • Cell Proliferation/drug effects
  • Down-Regulation/drug effects
  • Fibroblast Growth Factors/metabolism
  • Hair Cells, Auditory/drug effects
  • Hair Cells, Auditory/metabolism*
  • Histone Demethylases/metabolism*
  • In Situ Hybridization
  • Larva/drug effects
  • Larva/metabolism
  • Lateral Line System/drug effects
  • Lateral Line System/metabolism
  • Mitosis/drug effects
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Regeneration*/drug effects
  • Tranylcypromine/pharmacology
  • Wnt Signaling Pathway/drug effects
  • Zebrafish/embryology
  • Zebrafish/metabolism*
  • Zebrafish Proteins/metabolism*
PubMed: 26008620 Full text @ Mol. Neurobiol.
ABSTRACT
Lysine-specific demethylase 1 (LSD1/KDM1A) plays an important role in complex cellular processes such as differentiation, proliferation, apoptosis, and cell cycle progression. It has recently been demonstrated that during development, downregulation of LSD1 inhibits cell proliferation, modulates the expression of cell cycle regulators, and reduces hair cell formation in the zebrafish lateral line, which suggests that LSD1-mediated epigenetic regulation plays a key role in the development of hair cells. However, the role of LSD1 in hair cell regeneration after hair cell loss remains poorly understood. Here, we demonstrate the effect of LSD1 on hair cell regeneration following neomycin-induced hair cell loss. We show that the LSD1 inhibitor trans-2-phenylcyclopropylamine (2-PCPA) significantly decreases the regeneration of hair cells in zebrafish after neomycin damage. In addition, immunofluorescent staining demonstrates that 2-PCPA administration suppresses supporting cell proliferation and alters cell cycle progression. Finally, in situ hybridization shows that 2-PCPA significantly downregulates the expression of genes related to Wnt/β-catenin and Fgf activation. Altogether, our data suggest that downregulation of LSD1 significantly decreases hair cell regeneration after neomycin-induced hair cell loss through inactivation of the Wnt/β-catenin and Fgf signaling pathways. Thus, LSD1 plays a critical role in hair cell regeneration and might represent a novel biomarker and potential therapeutic approach for the treatment of hearing loss.
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