An in vivo Look at Vertebrate Liver Architecture: Three‐Dimensional Reconstructions from Medaka (Oryzias latipes)

Abstract

Understanding three-dimensional (3D) hepatobiliary architecture is fundamental to elucidating structure/function relationships relevant to hepatobiliary metabolism, transport, and toxicity. To date, factual information on vertebrate liver architecture in 3 dimensions has remained limited. Applying noninvasive in vivo imaging to a living small fish animal model we elucidated, and present here, the 3D architecture of this lower vertebrate liver. Our investigations show that hepatobiliary architecture in medaka is based on a polyhedral (hexagonal) structural motif, that the intrahepatic biliary system is an interconnected network of canaliculi and bile-preductules, and that parenchymal architecture in this lower vertebrate is more related to that of the mammalian liver than previously believed. The in vivo findings presented advance our comparative 3D understanding of vertebrate liver structure/function, help clarify previous discrepancies among vertebrate liver conceptual models, and pose interesting questions regarding the ''functional unit'' of the vertebrate liver. Anat Rec, 290:770-782, 2007. 2007 Wiley-Liss, Inc.

Non invasive high resolution in vivo imaging of α-naphthylisothiocyanate (ANIT) induced hepatobiliary toxicity in STII medaka

“…See-through (STII) medaka are homozygous recessive for all four pigments (iridophores, leucophores, xanthophores, melanophores). Exhibiting no expression of leucophores and melanophores, and minimal expression of xanthophores and iridiophores, STII medaka are essentially transparent throughout their life cycle (Wakamatsu et al 2001), and allow high resolution (< 1μm) non invasive in vivo imaging of internal organs and tissues at the subcellular level ( Figure 1) (Hardman et al 2007a;Hardman et al 2007b;Hinton et al 2004). Our STII medaka colony, maintained at Duke University since 2002, was first cultured with stock obtained from Prof. Y. Wakamatsu (Nagoya University).…”

“…We know comparatively less about the piscine biliary system, though are we gaining greater insight into piscine hepatobiliary structure/function relationships (Ballatori et al 1999;Ballatori et al 2000;Boyer et al 1976a;Boyer et al 1976b;Hampton et al 1989;Hampton JA 1988;Hardman et al 2007b;Hinton et al 1987;Hinton et al 2001;Rocha et al 2001;Rocha et al 1997). Because our understanding of the piscine biliary system has lagged, particularly in a comparative sense, our ability to interpret and communicate biliary disease and toxicity in piscine species has been limited.…”

“…impaired mitochondrial function, necrosis), cholestasis (Hill and Roth 1998;Orsler et al 1999;Waters et al 2002;Woolley et al 1979), and biliary tree arborization (biliary epithelial cell hyperplasia) (Alpini et al 1992;Connolly et al 1988;Masyuk et al 2003). Because biliary toxicity and cholestasis are poorly understood in piscine species, and because we now understand the medaka hepatobiliary system to be more similar to mammalian liver architecture than previously considered (Hardman et al 2007b), we considered ANIT good toxicant for investigation of comparative hepatology. The goals of these investigations were to determine the cellular targets of ANIT in medaka and to characterize toxic response, relative to what is known regarding ANIT induced hepatotoxicity in mammalian liver.…”

“…More recent in vivo investigations in STII medaka that elucidated structure/function relationships in both 2 and 3 dimensional contexts revealed medaka livers to be replete with bile preductular epithelial cells (BPDECs), and the transitional biliary passageways (bile preductules, BPDs) associated with them (Hardman et al 2007a;Hardman et al 2007b). These investigations revealed that the intrahepatic biliary system in medaka is largely an interconnected network of equidiameter (1-2 μm) canaliculi and bile preductules, organized through a polyhedral (hexagonal) structural motif, that occupies the majority of the liver corpus (~95%) uniformly.…”

“…Previous studies from this laboratory have shown the hepatobiliary systems of channel catfish (Ictalurus punctatus), trout (Oncorhynchus mykiss), and medaka (Oryzias latipes) to exhibit numerous transitional biliary passageways, termed bile preductules, between hepatocellular canaliculi and biliary epithelial cell (BEC) delimited bile ductules (Hampton JA 1988;Hardman et al 2007b;Okihiro and Hinton 2000). These transitional biliary passageways, first described in the mammalian liver by Steiner and Carruthers (1961), are anatomically associated with peri-portal canals of Hering and oval cells in the mammalian liver (Fausto 2000;Fausto and Campbell 2003;Golding et al 1996;Theise et al 1999).…”