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Discussion
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
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