The effects of methylmercury on Notch signaling during embryonic neural development in Drosophila melanogaster
| Autor: | Matthew D. Rand, Gregory L. Engel, Anton Delwig |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Embryo
Nonmammalian Notch signaling pathway Embryonic Development Toxicology Article Cell Line Downregulation and upregulation otorhinolaryngologic diseases Basic Helix-Loop-Helix Transcription Factors Animals Drosophila Proteins Enhancer Genetics Neurons biology Receptors Notch musculoskeletal neural and ocular physiology Gene Expression Regulation Developmental General Medicine Methylmercury Compounds biology.organism_classification Phenotype Cell biology Up-Regulation Repressor Proteins Drosophila melanogaster sense organs Signal transduction Neural development Drosophila Protein psychological phenomena and processes Signal Transduction |
| Zdroj: | Toxicology in vitro : an international journal published in association with BIBRA. 26(3) |
| ISSN: | 1879-3177 |
| Popis: | Methylmercury (MeHg) is a ubiquitous toxicant that targets the developing fetal nervous system. MeHg interacts with the Notch signaling pathway, a highly-conserved intercellular signaling mechanism required for normal development. Notch signaling is conveyed by activation of the genes in the enhancer of split (E(spl)) locus in Drosophila. We have previously shown that acute high doses of MeHg upregulate several E(spl) genes in Drosophila neural-derived C6 cells. Furthermore, MeHg induction of E(spl) can occur independent of the Notch receptor itself. We now show that MeHg, unlike inorganic mercury (HgCl2), preferentially upregulates E(spl)mδ and E(spl)mγ in Drosophila C6 cells. This is distinct from Delta ligand-induced Notch signaling in which no induction of E(spl)mδ is seen. MeHg is also seen to specifically upregulate E(spl)mδ in Drosophila embryos where HgCl2 showed no such effect. Additionally, treatment of embryos with MeHg caused a consistent failure in axonal outgrowth of the intersegmental nerve (ISN). This ISN phenotype was partially replicated by genetic activation of the Notch pathway, but was not replicated by increasing expression of E(spl)mδ. These data suggest a role for Notch signaling and the E(spl)mδ target gene in MeHg toxicity, however, the site of action for E(spl)mδ in this system remains to be elucidated. |
| Databáze: | OpenAIRE |
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