Dynamic three‐dimensional morphogenesis of intrahepatic bile ducts in mouse liver development

Takashima, Yasuo; Terada, Maiko; Kawabata, Masuyo; Suzuki, Atsushi

doi:10.1002/hep.27436

Cited by 46 publications

(56 citation statements)

References 30 publications

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“…In a recent study, a similar 3D morphometric approach has been used efficiently to understand the morphogenesis of bile ducts during embryonic development . The authors report that duct formation occurs through initial formation of precursor cell clusters, which next elongate to form segments and finally fuse to generate a de novo bile duct including all its branches.…”

Section: Discussionmentioning

confidence: 99%

Cholestasis‐induced adaptive remodeling of interlobular bile ducts

et al. 2016

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Cholestasis is a common complication in liver diseases that triggers a proliferative response of the biliary tree. Bile duct ligation (BDL) is a frequently used model of cholestasis in rodents. To determine which changes occur in the three‐dimensional (3D) architecture of the interlobular bile duct during cholestasis, we used 3D confocal imaging, surface reconstructions, and automated image quantification covering a period up to 28 days after BDL. We show a highly reproducible sequence of interlobular duct remodeling, where cholangiocyte proliferation initially causes corrugation of the luminal duct surface, leading to an approximately five‐fold increase in surface area. This is analogous to the function of villi in the intestine or sulci in the brain, where an expansion of area is achieved within a restricted volume. The increase in surface area is further enhanced by duct branching, branch elongation, and loop formation through self‐joining, whereby an initially relatively sparse mesh surrounding the portal vein becomes five‐fold denser through elongation, corrugation, and ramification. The number of connections between the bile duct and the lobular bile canalicular network by the canals of Hering decreases proportionally to the increase in bile duct length, suggesting that no novel connections are established. The diameter of the interlobular bile duct remains constant after BDL, a response that is qualitatively distinct from that of large bile ducts, which tend to enlarge their diameters. Therefore, volume enhancement is only due to net elongation of the ducts. Because curvature and tortuosity of the bile duct are unaltered, this enlargement of the biliary tree is caused by branching and not by convolution. Conclusion: BDL causes adaptive remodeling that aims at optimizing the intraluminal surface area by way of corrugation and branching. (Hepatology 2016;63:951–964)

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Section: Discussionmentioning

confidence: 99%

Cholestasis‐induced adaptive remodeling of interlobular bile ducts

et al. 2016

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“…49 The ductal plate is a bilayered tubular structure surrounded by thick mesenchyme that is formed near the portal vein between 11 and 13 weeks of gestation. 50 The plate gradually disappears, except for a focal area where it forms a lumen and gives rise to intrahepatic bile ducts; 51 its postnatal persistence raises the possibility that abnormal mesenchymal and cholangiocyte signals halt remodelling of hilar ducts. Although ductal plate malformation has been described in infants with the embryonic form of biliary atresia, a study of the morphology of several portal tracts from each of eight infants with the perinatal form of biliary atresia and six with BASM identified ductal plate malformation in only 10% of the portal tracts, with no predilection to either clinical forms of the disease.…”

Section: Pathogenic Mechanisms Of Diseasementioning

confidence: 99%

Pathogenesis of biliary atresia: defining biology to understand clinical phenotypes

Asai

Miethke

Bezerra

2015

Nat Rev Gastroenterol Hepatol

233

223

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Biliary atresia is a severe cholangiopathy of early infancy that destroys extrahepatic bile ducts and disrupts bile flow. With a poorly defined disease pathogenesis, treatment consists of the surgical removal of duct remnants followed by hepatoportoenterostomy. Although this approach can improve the short-term outcome, the liver disease progresses to end-stage cirrhosis in most children. Further improvement in outcome will require a greater understanding of the mechanisms of biliary injury and fibrosis. Here, we review progress in the field, which has been fuelled by collaborative studies in larger patient cohorts and the development of cell culture and animal model systems to directly test hypotheses. Advances include the identification of phenotypic subgroups and stages of disease based on clinical, pathological and molecular features. Stronger evidence exists for viruses, toxins and gene sequence variations in the aetiology of biliary atresia, triggering a proinflammatory response that injures the duct epithelium and produces a rapidly progressive cholangiopathy. The immune response also activates the expression of type 2 cytokines that promote epithelial cell proliferation and extracellular matrix production by nonparenchymal cells. These advances provide insight into phenotype variability and might be relevant to the design of personalized trials to block progression of liver disease.

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“…Recently, Takashima et al. obtained 2D images of IHBD obtained from serial liver sections and reconstituted them into the 3D images . Kaneko et al.…”

Section: Development Of Ihbdmentioning

confidence: 99%

Morphogenesis of liver epithelial cells

Tanimizu

Mitaka

2016

Hepatology Research

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The mammalian liver is a physiologically important organ performing various types of metabolism, producing serum proteins, detoxifying bilirubin and ammonia, and protecting the body from infection. Those physiological functions are achieved with the 3D tissue architecture of liver epithelial cells. The liver contains two types of epithelial cells, namely, hepatocytes and cholangiocytes. They split from hepatoblasts (embryonic liver stem cells) in mid-gestation and differentiate into structurally and functionally mature cells. Analyses of mutant mice showing abnormal liver organogenesis have identified genes involved in liver development. In vitro culture systems have been used to examine the mechanism in which each molecule or signaling pathway regulates the morphogenesis and functional differentiation of hepatocytes and cholangiocytes. In addition, liver epithelial cells as well as mesenchymal, sinusoidal endothelial and hematopoietic cells can be purified from developing livers, which enables us to perform genome-wide screening to identify novel genes regulating epithelial morphogenesis in the liver. By combining these in vivo and in vitro systems, the liver could be a unique and suitable model for revealing a principle, governing epithelial morphogenesis. In this review, we summarize recent progress in the understanding of the development of liver epithelial tissue structures.

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Dynamic three‐dimensional morphogenesis of intrahepatic bile ducts in mouse liver development

Cited by 46 publications

References 30 publications

Cholestasis‐induced adaptive remodeling of interlobular bile ducts

Cholestasis‐induced adaptive remodeling of interlobular bile ducts

Pathogenesis of biliary atresia: defining biology to understand clinical phenotypes

Morphogenesis of liver epithelial cells

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