Changes of biliary cilia, smooth muscle tissue distribution, innervation and extracellular matrices during morphological evolution of hepatic architectures in vertebrates.

BACKGROUND: The liver architecture of vertebrates can be classified into two types, the portal triad type (having periportal bile ducts) and the non-portal triad type (having bile ducts independent of the course of portal veins). The former is typically detectable in livers of tetrapods and cartilaginous fish, and its ancestral state is found in the hagfish, an earliest diverged lineage among vertebrates. Teleosts other than osteoglossomorphs have the latter. The aim of the present study is to reveal the changes of the hepatic innervation, biliary cilia and smooth muscle distribution, and extracellular matrices along vertebrate evolution with attention to the two types of liver architectures. METHODS: The hepatic innervation, biliary cilia and smooth muscle distribution, and collagen deposition were immunohistochemically and histochemically compared among livers of various vertebrates, using anti-acetylated tubulin and anti-α-smooth muscle actin antibodies, and Sirius red staining. These were also ultrastructurally examined. RESULTS: Although the hagfish liver had periportal intrahepatic bile ducts and ductules as detected in mammalian livers, it lacked smooth muscles around bile ducts and portal veins. Extracellular matrices in their connective tissues had thick collagen fibers. Its innervation was restricted to intrahepatic bile ducts and portal veins in the hilum. In livers of other vertebrates, including teleosts, the innervation was broadly detectable, especially around bile ducts, hepatic arteries and portal veins (afferent vessels), but not around central veins (efferent vessels). The chondrichthyans ultrastructurally had smooth muscle tissue around bile ducts. Cilia distribution was confirmed in intrahepatic bile ducts of tetrapods and basal actinopterygians. Teleosts other than osteoglossomorphs lacked cilia in their intrahepatic bile ducts. CONCLUSIONS: The liver architecture of the hagfish may be unique for innervation and extracellular matrices. Hepatic innervation may not have occurred in vertebrate ancestors. Hepatic innervation in bile ducts, hepatic arteries and portal veins may have been conserved among the extant jawed vertebrates. Cilia distribution in bile ducts may have changed during evolution of actinopterygians.

Phylogenetic analyses of the hepatic architecture in vertebrates.

The mammalian liver has a structural and functional unit called the liver lobule, in the periphery of which the portal triad consisting of the portal vein, bile duct and hepatic artery is developed. This type of hepatic architecture is detectable in many other vertebrates, including amphibians and birds, whereas intrahepatic bile ducts run independently of portal vein distribution in actinopterygians such as the salmon and tilapia. It remains to be clarified how the hepatic architectures are phylogenetically developed among vertebrates. The present study morphologically and immunohistochemically analyzed the hepatic structures of various vertebrates, including as many classes and subclasses as possible, with reference to intrahepatic bile duct distribution. The livers of vertebrates belonging to the Agnatha, Chondrichthyes, Amphibia, Aves, Mammalia, and Actinopterygii before Elopomorpha, had the portal triad-type architecture. The Anguilliformes livers developed both periportal bile ducts and non-periportal bile ducts. The Otocephala and Euteleostei livers had independent configuration of bile ducts and portal veins. Pancreatic tissues penetrated the liver parenchyma along portal veins in the Euteleostei. The liver of the lungfish, which shares the same origin with amphibians, did not have the portal triad-type architecture. Teleostei and lungfish livers had ductular development in the liver parenchyma similar to oval cell proliferation in injured mammalian livers. Euteleostei livers had penetration of significant numbers of independent portal veins from their intestines, suggesting that each liver lobe might receive a different blood supply. The hepatic architectures of the portal triad-type changed to non-portal triad-type architecture along the evolution of the Actinopterygii. The hepatic architecture of the lungfish resembles that of the Actinopterygii after Elopomorpha in intrahepatic biliary configuration, which may be an example of convergent evolution.