Light and Electron Microscopic Studies on the Development of Periportal Bile Ducts of the Human Embryo

Enzan, Hideaki; Ohkita, Takeshi; Fujita, Hisao; Iijima, Soichi

doi:10.1111/j.1440-1827.1974.tb00835.x

Cited by 20 publications

(19 citation statements)

References 12 publications

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“…There fore, bile ductular proliferation represents a feature of the chronic inflammatory disease occurring as the result of tubularization of hepatocytic cords. These results further support the concept that bile duct cells originate from hepatocytes [7,[16][17][18][19][20][21][22].…”

Section: Discussionsupporting

confidence: 79%

Expression and Distribution of a Human Colon-Carcinoma-Associated Antigen in Normal and Diseased Liver Tissue

Sansonno

Dammacco

1993

Pathobiology

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Expression and distribution of 17-1 A, a human colon-carcinoma-associated antigen as defined by a monoclonal antibody (17-1A mAb), were evaluated in liver tissues from normal subjects and patients with inflammatory and noninflammatory liver diseases. The antigen recognized by 17-1A mAb is a 41-kD protein that does not belong to the proteins of the cytoskeleton. Using a streptavidin-biotin-peroxidase method on frozen sections of liver tissue, it was located in the cytoplasm of bile duct epithelial cells in normal livers, whereas the hepatocytes were completely unreactive. When diseased liver tissue was examined, a strong 17-1A Ag expression was demonstrable in the epithelium of typical and atypical bile ductules in portal areas. In addition, periportal or periseptal hepatocytes revealed variable staining for 17-1A Ag directly related to acute and chronic inflammatory changes. 17-1A Ag expression in hepatocytes reached the highest frequency in acute hepatitis (5/5) and chronic active hepatitis (17/19). These results indicate that periportal hepatocytes are capable of acquiring antigen expression common to bile ductular cells in inflammatory liver diseases, further supporting the view that these ductules represent transformed hepatocytes. Furthermore, two distinct pictures were found in primary liver malignancies. Neoplastic bile duct epithelium did not maintain 17-1A Ag expression in cholangiocarcinoma, whereas neoplastic liver cells acquired cytoplasmic 17-1A Ag expression in clustered areas in hepatocellular carcinoma and the intensity of staining and antigen distribution were inversely related to the grade of tumor differentiation.

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Section: Discussionsupporting

confidence: 79%

Expression and Distribution of a Human Colon-Carcinoma-Associated Antigen in Normal and Diseased Liver Tissue

Sansonno

Dammacco

1993

Pathobiology

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“…The ECM components in the connective tissue surrounding the portal vein appear to be important for the development of the IHBDs (Wilson et al, 1963;Enzan et al, 1974;Shiojiri, 1984). Connective tissue expresses fibronectin and type I collagen, suggesting that these proteins might be involved in the development of the IHBDs (Baloch et al, 1992).…”

Section: Ecm Components Are Important For the Differentiation Of The mentioning

confidence: 99%

“…BECs originate from bipotential hepatoblasts, which can also differentiate into mature hepatocytes (Shah and Gerber, 1989;Shiojiri, 1994;Haruna et al, 1996). The portal mesenchyme is believed to induce hepatoblasts to differentiate into BECs (Wilson et al, 1963;Wood, 1965;Enzan et al, 1974;Shiojiri, 1984). Major components of the extracellular matrix (ECM) of the portal mesenchyme, such as collagen, fibronectin, and laminin, may be involved in the induction of bile duct differentiation (Shah and Gerber, 1990;Baloch et al, 1992;Shiojiri and Nagai, 1992;Terada and Nakanuma, 1994).…”

Section: Introductionmentioning

confidence: 99%

FGF signaling segregates biliary cell‐lineage from chick hepatoblasts cooperatively with BMP4 and ECM components in vitro

Yanai

Tatsumi

Hasunuma

et al. 2008

Developmental Dynamics

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Intrahepatic bile ducts (IHBDs) are indispensable for transporting bile secreted from hepatocytes to the hepatic duct. The biliary epithelial cells (BECs) of the IHBD arise from bipotent hepatoblasts around the portal vein, suggesting the portal mesenchyme is essential for their development. However, except for Notch or Activin/ TGF-␤ signaling molecules, it is not known which molecules regulate IHBD development. Here, we found that FGF receptors and BMP4 are specifically expressed in the developing IHBD and the hepatic mesenchyme, respectively. Using a mesenchyme-free culture of liver bud, we showed that bFGF and FGF7 induce the hepatoblasts to differentiate into BECs, and that BMP4 enhances bFGF-induced BEC differentiation. The extracellular matrix (ECM) components in the hepatic mesenchyme induced BEC differentiation. Forced expression of a constitutively active form of the FGF receptor partially induced BEC differentiation markers in vivo. These data strongly suggest that bFGF and FGF7 promote BEC differentiation cooperatively with BMP4 and ECMs in vivo.

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“…It is well established that bile duct differentiation by hepatoblasts takes place in periportal areas in the fetal stages of humans and rodents (Bloom, 1926;Enzan et al, 1974;Haruna et al, 1996;Horstmann, 1939;Shiojiri, 1981Shiojiri, , 1994Shiojiri et al, 1991;Terada et al, 1998;Terada and Nakanuma, 1994;Van Eyken et al, 1988a, 1988b. Immunohistochemical studies have shown that hepatoblasts are a homogeneous population in terms of expression of alpha-fetoprotein, albumin, and cytokeratins before the appearance of periportal bile duct progenitors (Shiojiri, 1981;Shiojiri et al, 1991;Van Eyken et al, 1988a, 1988b.…”

Section: Discussionmentioning

confidence: 99%

“…Biliary epithelial cells differentiate from a histochemically homogeneous cell population of hepatoblasts under the influence of periportal connective tissue at the fetal stage, and other hepatoblasts give rise to mature hepatocytes during mammalian liver development (Bloom, 1926;Enzan et al, 1974;Haruna et al, 1996;Horstmann, 1939;Shiojiri, 1994;Shiojiri et al, 1991;Terada et al, 1998;Terada and Nakanuma, 1994;Van Eyken et al, 1988a, 1988b. It has also been experimentally demonstrated that hepatoblasts can give rise to both hepatocytes and biliary epithelial cells during in vivo transplantation experiments using immature fetal mouse liver fragments (Shiojiri, 1984;Shiojiri et al, 1995).…”

mentioning

confidence: 99%

Cell Lineage Analysis during Liver Development Using the spfash-Heterozygous Mouse

Shiojiri

Inujima

Ishikawa

et al. 2001

Laboratory Investigation

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SUMMARY:Biliary epithelial cells differentiate from periportal hepatoblasts during fetal mouse liver development. It remains to be determined whether each hepatoblast is equivalent for differentiation into hepatocytes and biliary epithelial cells in normal liver development. To resolve this question, the mosaic pattern of ornithine transcarbamylase (OTC) expression was analyzed in the hepatoblast population of spf ash (sparse-fur with abnormal skin and hair)-heterozygous fetal mouse livers, in which random inactivation of either the X chromosome carrying the spf ash gene (causing OTC deficiency) or its wild-type gene occurs. Aggregates (patches) of OTC-positive hepatoblasts showed very complex patterns, and their shapes and size distributions were similar in sections from periportal regions and nonperiportal regions of the fetal liver in which bile duct differentiation by periportal hepatoblasts occurred. Average sizes of periportal patches were larger than those of nonperiportal patches because of the presence of more hemopoietic cells in the latter region. The OTC mosaicism in periportal bile duct progenitors and hepatoblast islands of other liver parenchyma was also similar. These results suggest that the growth patterns of hepatoblasts are similar in both periportal and nonperiportal regions. Isolated three-dimensional patches comprising hepatoblasts giving rise to only biliary epithelial cells or hepatoblasts giving rise to both hepatocytes and biliary epithelial cells were observed in periportal regions. In nonperiportal regions, patches consisting of hepatoblasts differentiating into hepatocytes were also seen. Thus, it is likely that there are three lineages for the developmental fates of hepatoblasts: hepatoblasts giving rise to only biliary epithelial cells, hepatoblasts giving rise to only hepatocytes, and hepatoblasts giving rise to both of them. (Lab Invest 2001, 81:17-25).

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Light and Electron Microscopic Studies on the Development of Periportal Bile Ducts of the Human Embryo

Cited by 20 publications

References 12 publications

Expression and Distribution of a Human Colon-Carcinoma-Associated Antigen in Normal and Diseased Liver Tissue

Expression and Distribution of a Human Colon-Carcinoma-Associated Antigen in Normal and Diseased Liver Tissue

FGF signaling segregates biliary cell‐lineage from chick hepatoblasts cooperatively with BMP4 and ECM components in vitro

Cell Lineage Analysis during Liver Development Using the spfash-Heterozygous Mouse

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