1 2 3 4 5 6 7 8


In this study, we tested the hypothesis that valproic acid acts in a similar manner across the chordate phylum by down-regulating Pax-1 gene expression and causing a number of skeletal malformations. The treatment of zebrafish embryos with valproic acid led to the formation of a number of somite anomalies including discrete somite fusion and mis-segmentations as seen in previous studies by Barnes et. al. (1996). These anomalies are consistent with the types of axial skeletal defects previously reported in embryos of other organisms exposed to valproic acid, including wavy or fused ribs. Also, valproic acid led to other somite anomalies in some embryos, including randomized or scrambled somite patterns. We also observed that the concentration of valproic acid alters the effects of valproic acid. At lower dosages, 0.025M and 0.05M, few somite abnormalities occur, while at high dosages, 0.1M and 0.2M, embryonic mortality increased as well as the number of somite anomalies created. The timing of valproic acid treatment also had an effect on the results. Embryos treated with valproic acid prior to the mid-blastula transition (10th cell division) did not survive long enough to develop somites, but those embryos treated after the transition had a higher survival rate. While this experiment did not directly test for Pax-1 expression, it can be deduced that Pax-1 expression was down-regulated. Embryos treated with valproic acid resulted in similar somite abnormalities as compared to embryos of other animals in which Pax-1 expression was specifically tested for. Therefore, similarly to other chordates, zebrafish exhibit pattern-forming genes that can be altered by teratogens. Specifically, the teratogen valproic acid caused a number of somite abnormalities in zebrafish which can be linked to the down-regulation of the Pax-1 gene.

© Cebra-Thomas, 2001

Last Modified: 31 May 2001

[Lab Protocols | Students | Cebra-Thomas | Course | Links ]