Ueno Tomoya, Ishihara Akinori, Yagi Shinomi, Koike Toru, Yamauchi Kiyoshi, Shiojiri Nobuyoshi
Department of Biology, Faculty of Science, Shizuoka University, Oya 836, Suruga-ku, Shizuoka City, Shizuoka 422-8529, Japan.
Zoolog Sci. 2015 Jan;32(1):88-96. doi: 10.2108/zs140104.
In mammalian liver development, intrahepatic biliary morphogenesis takes place in periportal, but not in pericentral, regions. Liver progenitor cells transiently form epithelial plate structures and then intrahepatic bile ducts around the portal veins under the influence of the mesenchyme. The present study was undertaken to histochemically examine normal biliary development and its dependence on the action of the thyroid hormone triiodothyronine (T3) in Xenopus laevis tadpoles. In these tadpoles, the development of hepatic ducts and intrahepatic biliary ducts commenced along the portal veins at NF stages 48-50 and stages 50-52, respectively, when the blood concentration of thyroid hormone may be still low. Some periportal hepatocytes expressed carbamoylphosphate synthase I and SOX9, which are hepatocyte and biliary cell markers, respectively, suggesting that periportal hepatocytes give rise to biliary epithelial cells. Periportal biliary cells did not form ductal plates, nor was the periportal mesenchyme well developed as seen in fetal mouse livers. jag1 mRNA was moderately expressed in cells of portal veins and biliary epithelial cells, and notch1 and notch2 mRNAs were weakly detectable in biliary epithelial cells during metamorphosis as seen in developing mammalian livers. These results suggest that Notch signaling plays a decisive role in biliary cell differentiation and morphogenesis of Xenopus tadpoles. Anti-thyroid agent treatment of the tadpoles resulted in delayed biliary morphogenesis, suggesting that biliary development may depend on T3. However, T3 treatment of the tadpoles did not enhance biliary development. Thus, T3 may act positively on biliary development at a very low concentration.
在哺乳动物肝脏发育过程中，肝内胆管形态发生发生在门静脉周围区域，而非中央静脉周围区域。肝祖细胞短暂形成上皮板结构，然后在间充质的影响下围绕门静脉形成肝内胆管。本研究旨在通过组织化学方法检查非洲爪蟾蝌蚪正常胆管发育及其对甲状腺激素三碘甲状腺原氨酸（T3）作用的依赖性。在这些蝌蚪中，肝管和肝内胆管的发育分别在NF阶段48 - 50和阶段50 - 52沿门静脉开始，此时甲状腺激素的血液浓度可能仍然很低。一些门静脉周围的肝细胞表达氨甲酰磷酸合成酶I和SOX9，它们分别是肝细胞和胆管细胞的标志物，这表明门静脉周围的肝细胞产生胆管上皮细胞。门静脉周围的胆管细胞没有形成导管板，门静脉周围的间充质也不像在胎鼠肝脏中那样发育良好。在变态过程中，jag1 mRNA在门静脉细胞和胆管上皮细胞中适度表达，notch1和notch2 mRNA在胆管上皮细胞中可微弱检测到，这与发育中的哺乳动物肝脏情况类似。这些结果表明Notch信号在非洲爪蟾蝌蚪胆管细胞分化和形态发生中起决定性作用。用抗甲状腺药物处理蝌蚪导致胆管形态发生延迟，这表明胆管发育可能依赖于T3。然而，用T3处理蝌蚪并没有促进胆管发育。因此，T3可能在非常低的浓度下对胆管发育起积极作用。
