Comparative study on a novel lobule structure of the zebrafish liver and that of the mammalian liver.

The mammalian liver has a lobule structure with a portal triad consisting of the portal vein, hepatic artery, and bile duct, which exhibits zonal gene expression, whereas those of teleosts do not have a portal triad. It remains to be demonstrated what kind of the unit structures they have, including their gene expression patterns. The aims of the present study were to demonstrate the unit structure of the teleost liver and discuss it in terms of evolution and adaptation in vertebrates and the use of teleosts as an alternative model for human disease. The zebrafish liver was examined as a representative of teleosts with respect to its morphological architecture and gene expression. A novel, polygonal lobule structure was detected in the zebrafish liver. In it, portal veins and central veins were distributed at the periphery and center, respectively. Sinusoids connected both veins. Anxa4-positive preductules were incorporated into the tubular lumen of two rows of hepatocytes in sections. Intrahepatic bile ducts resided randomly in the liver lobule. Zebrafish livers did not have zonal gene expression for metabolic pathways examined. The lobules of the zebrafish liver with preductules located in the tubular lumina of hepatocytes may resemble the oval cell reaction of injured livers of mammals and might convey bile to the intestine more safely than mammalian livers. The gene expression pattern in liver lobules and our liver lobule model of the zebrafish may be important to discuss data obtained in experiments using this animal as an alternative model for human disease.