PUBLICATION

Trans-2-phenylcyclopropylamine regulates zebrafish lateral line neuromast development mediated by depression of LSD1 activity

Authors
He, Y., Yu, H., Sun, S., Wang, Y., Liu, I., Chen, Z., and Li, H.
ID
ZDB-PUB-130805-23
Date
2013
Source
The International journal of developmental biology   57(5): 365-373 (Journal)
Registered Authors
Keywords
hair cell, LSD1, neuromast, trans-2-phenylcyclopropylamine, zebrafish
MeSH Terms
  • Methylation/drug effects
  • Histones/metabolism
  • Time Factors
  • Animals
  • Larva/drug effects
  • Larva/genetics
  • Larva/metabolism
  • Mechanoreceptors/drug effects*
  • Mechanoreceptors/metabolism
  • Mechanoreceptors/physiology
  • Tranylcypromine/pharmacology*
  • Blotting, Western
  • Reverse Transcriptase Polymerase Chain Reaction
  • Histone Demethylases/antagonists & inhibitors*
  • Histone Demethylases/genetics
  • Histone Demethylases/metabolism
  • Cell Proliferation/drug effects
  • Gene Expression Regulation, Developmental
  • Zebrafish Proteins/antagonists & inhibitors*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish/physiology*
  • Monoamine Oxidase Inhibitors/pharmacology
  • Apoptosis/drug effects
  • Lateral Line System/drug effects*
  • Lateral Line System/metabolism
  • Lateral Line System/physiology
  • Hair Cells, Auditory/drug effects
  • Hair Cells, Auditory/metabolism
  • Hair Cells, Auditory/physiology
(all 32)
PubMed
23873368 Full text @ Int. J. Dev. Biol.
Abstract

The zebrafish mechanosensory lateral line (LL) is a model system for the study of hair cell development, survival and regeneration. Recently, histone modifications have attracted a considerable amount of interest because of their indispensable roles in various kinds of cellular processes including differentiation, proliferation, apoptosis and function. Lysine specific demethylase 1 (LSD1) is an important enzyme that regulates histone methylation. As a transcriptional regulator, this enzyme has broad functional activities and is involved in many biological processes. However, the effects of LSD1 on the early development of zebrafish sensory system have not been fully elucidated. Here, we have found that pharmacological inhibition of LSD1 with the monoamine oxidase (MAO) inhibitor trans-2-phenylcyclopropylamine (referred to as 2-PCPA) reduced the numbers of both sensory hair cells and supporting cells of neuromasts during zebrafish development. Our results showed that the treatment of zebrafish larvae with 2-PCPA caused accumulation of histone methylation and suppressed proliferation of neuromast cells. Finally, acridine orange staining assay demonstrated that 2-PCPA treatment at high concentrations induced an enhancement of cellular apoptosis within neuromasts. Taken together, these results indicate that LSD1 demethylase activity is required for neuromast development in zebrafish larvae.

Genes / Markers
Figures
Figure Gallery (4 images)
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
s356tTgTransgenic Insertion
    1 - 1 of 1
    Show
    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    No data available
    Fish
    1 - 2 of 2
    Show
    Antibodies
    Name Type Antigen Genes Isotypes Host Organism
    Ab28-h3monoclonal
      Rabbit
      1 - 1 of 1
      Show
      Orthology
      No data available
      Engineered Foreign Genes
      Marker Marker Type Name
      GFPEFGGFP
      1 - 1 of 1
      Show
      Mapping
      No data available