Hepatocyte nuclear factor 4alpha controls the development of a hepatic epithelium and liver morphogenesis. Nat Genet 2003 Jul;34(3):292-6
Date
06/17/2003Pubmed ID
12808453DOI
10.1038/ng1175Scopus ID
2-s2.0-0038757830 (requires institutional sign-in at Scopus site) 517 CitationsAbstract
Although advances have been made in understanding cell differentiation, only rudimentary knowledge exists concerning how differentiated cells form tissues and organs. We studied liver organogenesis because the cell and tissue architecture of this organ is well defined. Approximately 60% of the adult liver consists of hepatocytes that are arranged as single-cell anastomosing plates extending from the portal region of the liver lobule toward the central vein. The basal surface of the hepatocytes is separated from adjacent sinusoidal endothelial cells by the space of Disse, where the exchange of substances between serum and hepatocytes takes place. The hepatocyte's apical surface forms bile canaliculi that transport bile to the hepatic ducts. Proper liver architecture is crucial for hepatic function and is commonly disrupted in disease states, including cirrhosis and hepatitis. Here we report that hepatocyte nuclear factor 4alpha (Hnf4alpha) is essential for morphological and functional differentiation of hepatocytes, accumulation of hepatic glycogen stores and generation of a hepatic epithelium. We show that Hnf4alpha is a dominant regulator of the epithelial phenotype because its ectopic expression in fibroblasts induces a mesenchymal-to-epithelial transition. Most importantly, the morphogenetic parameters controlled by Hnf4alpha in hepatocytes are essential for normal liver architecture, including the organization of the sinusoidal endothelium.
Author List
Parviz F, Matullo C, Garrison WD, Savatski L, Adamson JW, Ning G, Kaestner KH, Rossi JM, Zaret KS, Duncan SAMESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Cell Differentiation
Cell Division
Cells, Cultured
DNA-Binding Proteins
Epithelium
Female
Flow Cytometry
Gene Expression
Hepatocyte Nuclear Factor 4
Hepatocytes
Immunoblotting
Immunoenzyme Techniques
In Situ Nick-End Labeling
Liver
Liver Glycogen
Male
Mice
Mice, Knockout
Morphogenesis
Phosphoproteins
Pregnancy
Retroviridae
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factors
Transfection
