Molecular mechanisms which cause skeletal abnormalities in the jaw and gills
T. Suzuki and T. Kurokawa (Nutrition Div)
To reveal what factors induce skeletal malformation in larvae,
we analyzed the phenotypes of jaw anomalies experimentally by treatment with
retinoic acid. Accumulation of these kinds of data will make it possible to
predict the cause of skeletal abnormalities based on their phenotype.
- Larvae reproduced for aquaculture often have skeletal abnormalities
in the jaw, vertebrae and fins, which reduce not only the survival ratio but
also the commercial value. Even though skeletal abnormalities are attributable
to several factors such as excess vitamin A and high temperature, there is
little information on the mechanisms how these factors cause abnormalities.
So, we have been trying to reveal the molecular mechanisms that cause skeletal
- In most teleosts including flounder, the jaw and gill skeletal
structure develop in the early larval stage before first feeding, whereas
the vertebral skeletal structure forms in the late larval stage.
Therefore, the jaw and gill skeletal development is particularly
susceptible to the effects of maternal factors, such as vitamin A and its
active metabolite retinoic acid (RA) stocked in the yolk. RA is a key
molecule which controls embryogenesis by initiating mRNA expression of
transcriptional factors and signal proteins, such as Hox and sonic
hedgehog (shh) which regulate the differentiation of skeletal
precursor cells. In addition, excess RA is known to exert teratogenic
effects on skeleton. To reveal the teratogenic effect of RA on the jaw and
gill skeletal structure, we examined whether RA affects Hox and shh
expressions and what kind of abnormality is induced in the jaw and gill by
RA. When gastrulating embryos were incubated with RA, the anterior border
of the Hoxd-4 expression domain at both central nervous system and
pharyngeal area shifted anteriorly (Fig. 1A, B).
In such larvae, severe malformation such as fusion of skeletal elements
occurred in the lower jaw (Fig. 2A, B).
When flounder were exposed to RA in the late embryonic stage, the shh
expression in the jaw and gills was severely suppressed. The jaw and gill
skeletal structure grew downwards in larvae of which the shh
expression was affected by RA. Thus, different phenotypes of skeletal
abnormalities are caused by RA at each developmental stage. We are further
focusing on the mechanisms which cause malformation in the vertebrae and
- 1) Suzuki, T., Oohara, I., Kurokawa, T. (1999) Retinoic acid given at
late embryonic stage suppresses sonic hedgehog and Hoxd-4
expression in the pharyngeal area and induces skeletal malformation in
flounder (Paralichthys olivaceus) embryos. Develop. Growth Differ.
2) Suzuki, T., Srivastava, A. S., Kurokawa T. (2000) Experimental
induction of jaw, gill and pectoral fin malformations in Japanese
flounder, Paralichthys olivaceus, larvae. Aquaculture, 185,
- 3) Suzuki, T., Kurokawa T., Srivastava, A. S. (2001) Induction of bent
cartilaginous skeletons and undulating notochord in flounder embryos by
disulfiram and a, a-dipyridyl. Zool. Sci., 18, 345-351.
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