Transcriptomic profiling of mTOR and ryanodine receptor signaling molecules in developing zebrafish in the absence and presence of PCB 95

• Published in: PeerJ (San Francisco, CA) Vol. 5; p. e4106
• Main Authors: Frank, Daniel F, Miller, Galen W, Connon, Richard E, Geist, Juergen, Lein, Pamela J
• Format: Journal Article
• Language: English
• Published: United States PeerJ. Ltd 29.11.2017; PeerJ, Inc; PeerJ Inc
• Subjects: Artemia; Autism; Biological research; Biology; Cellular signal transduction; Cloning; Contaminants; Danio rerio; Developmental Biology; Embryos; Environmental factors; Environmental health; Fertilization; Fish; Genetic aspects; Kinases; mTOR; Nervous system; Neurodevelopmental disorders; Neuroscience; Neurotoxicity; Ontogeny; PCB; Persistent organic pollutants; Physiological aspects; Polychlorinated biphenyls; Rapamycin; Rodents; Ryanodine receptor; Ryanodine receptors; Signal transduction; TOR protein; Toxicology; Transcription; Transcription (Genetics); Transcriptomic profiling; Zebrafish; California; mTOR; Zebrafish; Neurodevelopmental disorders; Persistent organic pollutants; Transcriptomic profiling; Ryanodine receptor
• ISSN: 2167-8359; 2167-8359
• DOI: 10.7717/peerj.4106

The mechanistic target of rapamycin (mTOR) and ryanodine receptor (RyR) signaling pathways regulate fundamental processes of neurodevelopment, and genetic mutations within these pathways have been linked to neurodevelopmental disorders. While previous studies have established that these signaling molecules are expressed in developing zebrafish, a detailed characterization of the ontogenetic profile of these signaling molecules is lacking. Thus, we evaluated the spatiotemporal expression of key transcripts in mTOR and RyR signaling pathways in wildtype zebrafish at 24, 72 and 120 hours post fertilization (hpf). We further determined whether transcriptional profiles of a subset of genes in both pathways were altered by exposure to PCB 95 (2,2',3,5',6-pentachlorobiphenyl), a pervasive environmental contaminant known to cause developmental neurotoxicity in mammalian systems via RyR-dependent mechanisms. Quantitative PCR revealed that transcription generally increased across development. Genes in the signaling pathway upstream of the mTORC1 complex, and the RyR-paralogs, and , were robustly upregulated, and in situ hybridization of coincided with a transcriptional shift from muscle to neuronal tissue after 24 hpf. Static waterborne exposure to PCB 95 beginning at 6 hpf significantly altered transcription of genes in both pathways. These changes were concentration- and time-dependent, and included downregulation of , a member of the mTORC1 complex, at both 72 and 120 hpf, and increased transcript levels of the RyR paralog and downstream target of RyR signaling, Wingless-type 2ba ( ) at 72 hpf. The detailed transcriptomic profiling of key genes within these two signaling pathways provides a baseline for identifying other environmental factors that modify normal spatiotemporal expression patterns of mTOR and RyR signaling pathways in the developing zebrafish, as illustrated here for PCB 95.