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Rapid Evaluation of Toxicity of Chemical Compounds Using Zebrafish Embryos
Published on: August 25, 2019
Inhibition of embryonic development by microcystin-LR in zebrafish, Danio rerio
Pei-Jen Wang1, Ming-Shan Chien, Fong-June Wu
1Institute of Fisheries Science, National Taiwan University, Taipei, Taiwan, ROC.
Abstract:
Microcystin-LR (MC-LR), a cyanobacterial toxin, is a potent inhibitor of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A). PP1 and PP2A are critical regulators in embryonic development. However, the effects of MC-LR in embryonic development have been controversial. MC-LR has been demonstrated to be highly toxic in medaka, but not in zebrafish or rabbit embryos. The causes of difference may be due to membrane impermeability that impaired the delivery of MC-LR into cytoplasm of zebrafish and rabbit embryos. Therefore, we microinjected MC-LR directly into developing zebrafish embryos and investigated the effects of MC-LR on embryonic development. We demonstrated that MC-LR induced the lethality of zebrafish embryos in a dose- and time-dependent manner. MC-LR also induced the loss of blastomere coherence via the interference of beta-catenin and cadherins distributions. Furthermore, the MC-LR treated fry revealed various developmental defects. These results suggested that MC-LR might affect the phosphorylation equilibrium of signaling molecules, including beta-catenin and cadherins, required early in zebrafish embryonic development.
Insights
Microcystin-LR (MC-LR) causes zebrafish embryo lethality and developmental defects by disrupting cell adhesion proteins like beta-catenin and cadherins. Direct injection overcomes membrane impermeability, revealing MC-LR
Area of Science:
- Toxicology
- Developmental Biology
- Cell Biology
Background:
- Microcystin-LR (MC-LR) is a cyanobacterial toxin inhibiting protein phosphatases 1 and 2A.
- These phosphatases are crucial for embryonic development, but MC-LR's effects vary across species.
- Previous studies showed MC-LR toxicity in medaka but not zebrafish, possibly due to delivery issues.
Purpose of the Study:
- To investigate the direct effects of MC-LR on zebrafish embryonic development.
- To determine if MC-LR impacts blastomere coherence and signaling pathways in zebrafish embryos.
Main Methods:
- MC-LR was microinjected directly into developing zebrafish embryos.
- Dose- and time-dependent effects on lethality and development were assessed.
- Changes in beta-catenin and cadherin distribution were examined.
Main Results:
- MC-LR induced dose- and time-dependent lethality in zebrafish embryos.
- MC-LR disrupted blastomere coherence by altering beta-catenin and cadherin localization.
- Treated zebrafish fry exhibited significant developmental abnormalities.
Conclusions:
- Directly administered MC-LR is toxic to zebrafish embryos.
- MC-LR interferes with key cell adhesion molecules, impacting embryonic development.
- MC-LR may disrupt essential signaling pathways by altering protein phosphorylation in early zebrafish development.

