RRC ID 79075
Author Liu S, Kawanishi T, Shimada A, Ikeda N, Yamane M, Takeda H, Tasaki J.
Title Identification of an adverse outcome pathway (AOP) for chemical-induced craniofacial anomalies using the transgenic zebrafish model.
Journal Toxicol Sci
Abstract Craniofacial anomalies are one of the most frequent birth defects worldwide and are often caused by genetic and environmental factors such as pharmaceuticals and chemical agents. Although identifying adverse outcome pathways (AOPs) is a central issue for evaluating the teratogenicity, the AOP causing craniofacial anomalies has not been identified. Recently, zebrafish has gained interest as an emerging model for predicting teratogenicity because of high throughput, cost-effectiveness and availability of various tools for examining teratogenic mechanisms. Here, we established zebrafish sox10-EGFP reporter lines to visualize cranial neural crest cells (CNCCs) and have identified the AOPs for craniofacial anomalies. When we exposed the transgenic embryos to teratogens that were reported to cause craniofacial anomalies in mammals, CNCC migration and subsequent morphogenesis of the first pharyngeal arch were impaired at 24 hours post-fertilization. We also found that cell proliferation and apoptosis of the migratory CNCCs were disturbed, which would be key events of the AOP. From these results, we propose that our sox10-EGFP reporter lines serve as a valuable model for detecting craniofacial skeletal abnormalities, from early to late developmental stages. Given that the developmental process of CNCCs around this stage is highly conserved between zebrafish and mammals, our findings can be extrapolated to mammalian craniofacial development and thus help in predicting craniofacial anomalies in human.
Volume 196(1)
Pages 38-51
Published 2023-10-30
DOI 10.1093/toxsci/kfad078
PII 7235575
PMID 37531284
PMC PMC10614053
MeSH Adverse Outcome Pathways* Animals Gene Expression Regulation, Developmental Humans Mammals Skull Teratogens / pharmacology Zebrafish* / genetics Zebrafish* / metabolism
IF 3.703
Zebrafish RIKEN WT (RW)