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Developing the Zebrafish Neuromast Assay as a Predictive Toxicity Model
Citation:
Mirchandani, R., S. Thrikawala, C. Stephan, N. Nguyen, M. Sobieski, R. Judson, J. Gustafsson, AND M. Bondesson. Developing the Zebrafish Neuromast Assay as a Predictive Toxicity Model. Presented at Society of Toxicology, TX, San Antonio, March 11 - 15, 2018. https://doi.org/10.23645/epacomptox.7017488
Impact/Purpose:
Poster presentation at the 2018 SOT annual meeting. We aim to understand the developmental toxicity effects of environmental pollutants by using zebrafish embryos to identify compounds that negatively affect neuromasts of the lateral line, a system of tactile sense organ in fishes.
Description:
The vertebrate zebrafish (Danio rerio) embryo is an emerging model for screening for teratogenic compounds. We aim to understand the developmental toxicity effects of environmental pollutants by using zebrafish embryos to identify compounds that negatively affect neuromasts of the lateral line, a system of tactile sense organ in fishes. The zebrafish neuromasts are mechanoreceptors that responds to the flow of water, and are structurally and functionally similar to human inner ear hair cells. Neuromasts are positioned along the zebrafish body through migration of the neuromast primordium formed near the otic vesicle. Transgenic zebrafish embryos expressing fluorescence in neuromasts (GW57A) were used in a primary high throughput screen (HTS) of 294 compounds from EPA’s ToxCast phase I chemical inventory, primarily consisting of pesticides and antimicrobials. This generated a list of 48 potential hits that altered neuromast development and/or migration. These hits were re-screened with a higher number of replicates to confirm and characterize effects, and to determine the lowest effect levels (LELs). This resulted in 22 confirmed neuromast disruptors. A univariate analysis was performed on these 22 compounds to identify ToxCast in vitro assays that significantly correlated with the identified in vivo neuromast disruptors. Several assays for serotonin signaling were retained. In conclusion, our results identified several environmental pollutants with neuromast disrupting capacity. This suggests that the developing zebrafish embryo is an efficient in vivo model that can be used for rapid identification of compounds interfering with neuromast development and has the potential to be developed into a predictive toxicity model. This abstract does not necessarily reflect EPA policy.
URLs/Downloads:
DOI: Developing the Zebrafish Neuromast Assay as a Predictive Toxicity Model
MIRCHANDANI_RACHNA_GRASP2017.PDF (PDF, NA pp, 2504.309 KB, about PDF)