PUBLICATION

A systems biology approach reveals neuronal and muscle developmental defects after chronic exposure to ionising radiation in zebrafish

Authors
Murat El Houdigui, S., Adam-Guillermin, C., Loro, G., Arcanjo, C., Frelon, S., Floriani, M., Dubourg, N., Baudelet, E., Audebert, S., Camoin, L., Armant, O.
ID
ZDB-PUB-191231-8
Date
2019
Source
Scientific Reports   9: 20241 (Journal)
Registered Authors
Armant, Olivier
Keywords
none
Datasets
GEO:GSE134634
MeSH Terms
  • Animals
  • Antineoplastic Agents/pharmacology
  • Embryonic Development/drug effects
  • Embryonic Development/genetics
  • Embryonic Development/radiation effects*
  • Larva/drug effects
  • Larva/genetics
  • Larva/radiation effects
  • Muscle Development/drug effects
  • Muscle Development/genetics
  • Muscle Development/radiation effects*
  • Muscles/drug effects
  • Muscles/embryology
  • Muscles/radiation effects*
  • Nervous System/drug effects
  • Nervous System/embryology
  • Nervous System/radiation effects*
  • Radiation, Ionizing*
  • Systems Biology/methods*
  • Transcription Factors/genetics
  • Transcription Factors/metabolism
  • Transcriptome/drug effects
  • Transcriptome/radiation effects
  • Tretinoin/pharmacology
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
31882844 Full text @ Sci. Rep.
Abstract
Contamination of the environment after the Chernobyl and Fukushima Daiichi nuclear power plant (NPP) disasters led to the exposure of a large number of humans and wild animals to radioactive substances. However, the sub-lethal consequences induced by these absorbed radiological doses remain understudied and the long-term biological impacts largely unknown. We assessed the biological effects of chronic exposure to ionizing radiation (IR) on embryonic development by exposing zebrafish embryo from fertilization and up to 120 hours post-fertilization (hpf) at dose rates of 0.5 mGy/h, 5 mGy/h and 50 mGy/h, thereby encompassing the field of low dose rates defined at 6 mGy/h. Chronic exposure to IR altered larval behaviour in a light-dark locomotor test and affected cardiac activity at a dose rate as low as 0.5 mGy/h. The multi-omics analysis of transcriptome, proteome and transcription factor binding sites in the promoters of the deregulated genes, collectively points towards perturbations of neurogenesis, muscle development, and retinoic acid (RA) signaling after chronic exposure to IR. Whole-mount RNA in situ hybridization confirmed the impaired expression of the transcription factors her4.4 in the central nervous system and myogenin in the developing muscles of exposed embryos. At the organ level, the assessment of muscle histology by transmission electron microscopy (TEM) demonstrated myofibers disruption and altered neuromuscular junctions in exposed larvae at 5 mGy/h and 50 mGy/h. The integration of these multi-level data demonstrates that chronic exposure to low dose rates of IR has an impact on neuronal and muscle progenitor cells, that could lead to motility defects in free swimming larvae at 120 hpf. The mechanistic understanding of these effects allows us to propose a model where deregulation of RA signaling by chronic exposure to IR has pleiotropic effects on neurogenesis and muscle development.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes