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研究発表を行った学会；
・第４０回日本発生生物学会・第５９回日本細胞生物学会　合同大会、2007年 5月28~30日(福岡)

タイトル；The interaction between sinusoidal and hepatic epithelial cells mediated by Wnt9a/Frizzleds is required to regulate proliferation of the hepatic epithelium.
発表者；　松本　健　氏
　　　（熊本大学　発生医学研究センター　パターン形成分野）
Abstract；
The early vertebrate liver comprises hepatic parenchyma and sinusoidal cells. It has been reported that sinusoidal cells regulate growth and proliferation of the hepatic epithelial cells. However, the effect of sinusoidal cells on hepatic epithelial cells has not been determined. It is possible that (a) secreted molecule(s) derived from sinusoidal cells plays an important role in this interaction.
In the process of searching for the candidate genes for the molecule, we identified cWnt9a, which is expressed in sinusoidal cells during liver development. We found that cWnt9ais expressed in both endothelial and stellate cells. mRNAs encoding Frizzled-1,4,7, and 9, receptors for Wnt ligands, are detected in the hepatic epithelium in the early chick embryonic liver. In addition, immunoprecipitation experiment indicated that cWnt9awas able to bind to Frizzled-4, 7, and 9. We showed that overexpression of cWnt9aresults in an enlargement of the liver because of an increase of proliferating hepatoblasts. Conversely, inhibition of endogenous Wnt9afunction by RNA interference caused a reduction in the numbers of proliferating hepatoblasts, which correlated with an ~30% reduction in the amount of nuclear Beta-Catenin in the affected liver. These data suggest that cWnt9a/Beta-Catenin signaling directly regulates proliferation of hepatoblasts during early liver morphogenesis.
We concluded from these data that cWnt9a, which is expressed in sinusoidal cells, is required for proper liver development. These findings provide the first genetic evidence that interactions between hepatic epithelial cells and sinusoidal cells are mediated by Wnt9a/Frizzled signaling, and that the signaling regulates hepatic proliferation in early liver development.