Trimethyltin chloride inhibits neuronal cell differentiation in zebrafish embryo neurodevelopment

Kim, J., Kim, C.Y., Song, J., Oh, H., Kim, C.H., Park, J.H.
Neurotoxicology and teratology   54: 29-35 (Journal)
Registered Authors
Kim, Cheol-Hee, Park, Jae-Hak
Gene expression, Neurotoxicity, Trimethyltin chloride, Zebrafish
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Basic Helix-Loop-Helix Transcription Factors/genetics
  • Basic Helix-Loop-Helix Transcription Factors/metabolism
  • Cell Differentiation/drug effects*
  • Central Nervous System/drug effects*
  • Central Nervous System/embryology
  • Central Nervous System/growth & development
  • Dose-Response Relationship, Drug
  • ELAV-Like Protein 3/genetics
  • ELAV-Like Protein 3/metabolism
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/drug effects
  • Gene Expression Regulation, Developmental/drug effects*
  • Glial Fibrillary Acidic Protein
  • Hedgehog Proteins
  • Larva
  • Luminescent Proteins/genetics
  • Luminescent Proteins/metabolism
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism
  • Nestin/genetics
  • Nestin/metabolism
  • Neurons/drug effects*
  • RNA, Messenger/metabolism
  • Trimethyltin Compounds/pharmacology*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
26687135 Full text @ Neurotoxicol. Teratol.
Trimethyltin chloride (TMT) is a neurotoxicant widely present in the aquatic environment, primarily from effluents of the plastic industry. It is known to cause acute neuronal death in the limbic-cerebellar system, particularly in the hippocampus. However, relatively few studies have estimated the effects of TMT toxicity on neurodevelopment. In this study, we confirmed the dose-dependent effects of TMT on neurodevelopmental stages through analysis of morphological changes and fluorescence assays using HuC-GFP and olig2-dsRed transgenic zebrafish embryos. In addition, we analyzed the expression of genes and proteins related to neurodevelopment. Exposure of embryos to TMT for 4days post fertilization (dpf) elicited a concentration-related decrease in body length and increase in axial malformation. TMT affected the fluorescent CNS structure by decreasing pattern of HuC-GFP and olig2-dsRed transgenic zebrafish. In addition, it significantly modulated the expression patterns of Sonic hedgehog a (Shha), Neurogenin1 (Ngn1), Embryonic lethal abnormal vision like protein 3 (Elavl3), and Glial fibrillary acidic protein (Gfap). The overexpression of Shha and Ngn1, and downregulation of Elavl3 and Gfap, indicate repression of proneural cell differentiation. Our study demonstrates that TMT inhibits specific neurodevelopmental stages in zebrafish embryos and suggests a possible mechanism for the toxicity of TMT in vertebrate neurodevelopment.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes