Suppression of C/EBP alpha expression in biliary cell differentiation from hepatoblasts during mouse liver development

J Hepatol. 2004 Nov;41(5):790-8. doi: 10.1016/j.jhep.2004.07.011.


Background/aims: Intrahepatic biliary cell differentiation takes place in periportal hepatoblasts under the influence of the subjacent mesenchyme, which leads to the suppression of mature hepatocyte marker expression. This study was undertaken to analyze C/EBP alpha and beta expression, which may govern transcription of mature hepatocyte marker genes, during mouse liver development with special attention given to biliary differentiation.

Methods: Expression of C/EBP alpha and beta was immunohistochemically examined. Expression of alpha-fetoprotein, albumin and urea cycle enzymes, the genes of which have CCAAT motifs in their upstream regulatory sequences, was examined immunohistochemically or by using in situ hybridization.

Results: C/EBP alpha started to be expressed in endodermal cells of 9.5-day liver primordium, and continued to be expressed in hepatoblasts and hepatocytes throughout development. Although biliary cell progenitors transiently expressed mature hepatocyte markers, their expression of C/EBP alpha was weak or totally absent. The signals of C/EBP beta in hepatocytes were weak in fetal liver, but became stronger with postnatal development. Differentiated epithelial cells of intrahepatic biliary structures did not express C/EBP alpha.

Conclusions: These data suggest that the suppression of C/EBP alpha expression may be prerequisite to biliary cell differentiation in the hepatoblast population and one of its earliest signs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / genetics
  • Animals
  • Antibodies
  • Biliary Tract / cytology*
  • Biliary Tract / embryology*
  • CCAAT-Enhancer-Binding Protein-alpha / genetics*
  • CCAAT-Enhancer-Binding Protein-alpha / immunology
  • CCAAT-Enhancer-Binding Protein-alpha / metabolism
  • CCAAT-Enhancer-Binding Protein-beta / genetics
  • CCAAT-Enhancer-Binding Protein-beta / immunology
  • CCAAT-Enhancer-Binding Protein-beta / metabolism
  • Carbamoyl-Phosphate Synthase (Ammonia) / genetics
  • Cell Differentiation / physiology
  • Epithelial Cells / cytology
  • Female
  • Gene Expression Regulation, Developmental
  • Hepatocytes / cytology
  • Liver / cytology*
  • Liver / embryology*
  • Mice
  • Mice, Inbred C3H
  • Ornithine Carbamoyltransferase / genetics
  • Pregnancy
  • RNA, Messenger / analysis
  • alpha-Fetoproteins / genetics


  • Albumins
  • Antibodies
  • CCAAT-Enhancer-Binding Protein-alpha
  • CCAAT-Enhancer-Binding Protein-beta
  • RNA, Messenger
  • alpha-Fetoproteins
  • Ornithine Carbamoyltransferase
  • Carbamoyl-Phosphate Synthase (Ammonia)