Developmental toxicity screening in zebrafish

Abstract

Given the ever-increasing toxic exposure ubiquitously present in our environment as well as emerging evidence that these exposures are hazardous to human health, the current rodent-based regulations are proving inadequate. In the process of overhauling risk assessment methodology, a nonrodent test organism, the zebrafish, is emerging as tractable for medium- and high-throughput assessments, which may help to accelerate the restructuring of standards. Zebrafish have high developmental similarity to mammals in most aspects of embryo development, including early embryonic processes, and on cardiovascular, somite, muscular, skeletal, and neuronal systems. Here, we briefly describe the development of these systems and then chronicle the toxic impacts assessed following chemical exposure. We also compare the available data in zebrafish toxicity assays with two databases containing mammalian toxicity data. Finally, we identify gaps in our collective knowledge that are ripe for future studies.

Arsenic Exposure Inhibits Angiogenesis in Zebrafish via Downregulation of both VEGFA and VEGFR2

“…The notochord initiates angiogenic sprouting from these primary vessels by secreting sonic hedgehog (SHH), which upregulates vascular endothelial growth factor A (VEGFA) expression and secretion in adjacent myotomes. Secreted VEGFA is present in free (VEGFA121) and extracellular-matrix (ECM)-bound forms (VEGFA165 Arsenic (As), an environmental toxin, inhibits angiogenic ISV sprouting in zebrafish, resulting in shorter length, irregularly oriented, or entirely missing ISVs [2,7]. Our analyses of ISV growth dynamics showed that these changes result from decreased directed migration speed and perturbation of directional path-finding [7].…”

Using an Automated 3D-tracking System to Record Individual and Shoals of Adult Zebrafish

“…Zebrafish has become an important model for biological and pharmacological research [1][2][3] . Tracking of movement and spatial distribution patterns of individual zebrafish and of shoals of zebrafish is invaluable.…”

Visualization of Craniofacial Development in the sox10: kaede Transgenic Zebrafish Line Using Time-lapse Confocal Microscopy

“…It has many advantages, including small size, rapid and ex-utero embryonic development, and high breeding rates. Moreover, the embryo is optically transparent, making it amenable to observation of complex developmental events under the microscope 9 . It is an ideal animal model for the study of migration and differentiation of cranial neural crest cells.…”