Transcriptome Analysis of Chemically-Induced Sensory Neuron Ablation in Zebrafish

Cox, J.A., Zhang, B., Pope, H.M., Voigt, M.M.
PLoS One   11: e0148726 (Journal)
Registered Authors
Cox, Jane, Voigt, Mark, Zhang, Bo
Gene expression, Larvae, Sensory neurons, Axons, Neurons, RNA sequencing, Transcriptome analysis, Gene pool
MeSH Terms
  • Animals
  • Cytokines/biosynthesis
  • Cytokines/genetics
  • Denervation
  • Gene Expression Regulation, Developmental/drug effects*
  • Larva
  • Metabolic Networks and Pathways/genetics
  • Metronidazole/toxicity
  • Nerve Degeneration/chemically induced
  • Nerve Degeneration/genetics*
  • Nerve Fibers, Unmyelinated/drug effects
  • Nerve Tissue Proteins/biosynthesis*
  • Nerve Tissue Proteins/genetics
  • Neurogenesis/drug effects
  • Oxidoreductases/biosynthesis
  • Oxidoreductases/genetics
  • RNA, Messenger/biosynthesis
  • RNA, Messenger/genetics
  • Sensory Receptor Cells/drug effects*
  • Transcriptome*
  • Zebrafish/genetics*
  • Zebrafish/growth & development
  • Zebrafish Proteins/biosynthesis*
  • Zebrafish Proteins/genetics
26863206 Full text @ PLoS One
Peripheral glia are known to have a critical role in the initial response to axon damage and degeneration. However, little is known about the cellular responses of non-myelinating glia to nerve injury. In this study, we analyzed the transcriptomes of wild-type and mutant (lacking peripheral glia) zebrafish larvae that were treated with metronidazole. This treatment allowed us to conditionally and selectively ablate cranial sensory neurons whose axons are ensheathed only by non-myelinating glia. While transcripts representing over 27,000 genes were detected by RNAseq, only a small fraction (~1% of genes) were found to be differentially expressed in response to neuronal degeneration in either line at either 2 hrs or 5 hrs of metronidazole treatment. Analysis revealed that most expression changes (332 out of the total of 458 differentially expressed genes) occurred over a continuous period (from 2 to 5 hrs of metronidazole exposure), with a small number of genes showing changes limited to only the 2 hr (55 genes) or 5 hr (71 genes) time points. For genes with continuous alterations in expression, some of the most meaningful sets of enriched categories in the wild-type line were those involving the inflammatory TNF-alpha and IL6 signaling pathways, oxidoreductase activities and response to stress. Intriguingly, these changes were not observed in the mutant line. Indeed, cluster analysis indicated that the effects of metronidazole treatment on gene expression was heavily influenced by the presence or absence of glia, indicating that the peripheral non-myelinating glia play a significant role in the transcriptional response to sensory neuron degeneration. This is the first transcriptome study of metronidazole-induced neuronal death in zebrafish and the response of non-myelinating glia to sensory neuron degeneration. We believe this study provides important insight into the mechanisms by which non-myelinating glia react to neuronal death and degeneration in sensory circuits.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes