Mammalian hepatocyte differentiation requires the transcription factor HNF-4alpha. Genes Dev 2000 Feb 15;14(4):464-74
Date
02/26/2000Pubmed ID
10691738Pubmed Central ID
PMC316377Scopus ID
2-s2.0-0034090310 (requires institutional sign-in at Scopus site) 497 CitationsAbstract
HNF-4alpha is a transcription factor of the nuclear hormone receptor family that is expressed in the hepatic diverticulum at the onset of liver development. Mouse embryos lacking HNF-4alpha fail to complete gastrulation due to dysfunction of the visceral endoderm. This early embryonic lethality has so far prevented any analyses of the contribution of HNF-4alpha toward liver development and hepatocyte differentiation. However, we have shown that complementation of HNF-4alpha(-/-) embryos with a tetraploid embryo-derived wild-type visceral endoderm rescues this early developmental arrest and allows HNF-4alpha(-/-) embryos to proceed normally through midgestation stages of development. Examination of these rescued embryos revealed that HNF-4alpha was dispensable for specification and early development of the liver. However, HNF-4alpha(-/-) fetal livers failed to express a large array of genes whose expression in differentiated hepatocytes is essential for a functional hepatic parenchyma, including genes encoding several apolipoproteins, metabolic proteins, and serum factors. In addition, we have demonstrated that HNF-4alpha is essential for expression of the transcription factors HNF-1alpha and PXR within the fetal liver. We therefore conclude that HNF-4alpha is both essential for hepatocyte differentiation during mammalian liver development and also crucial for metabolic regulation and liver function.
Author List
Li J, Ning G, Duncan SAMESH terms used to index this publication - Major topics in bold
Acute-Phase ProteinsAnimals
Apolipoproteins
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Cell Aggregation
Cell Differentiation
Cells, Cultured
Coculture Techniques
DNA-Binding Proteins
Endoderm
Gastrula
Gene Expression Regulation, Developmental
Hepatocyte Nuclear Factor 4
Liver
Mice
Mice, Knockout
Phosphoproteins
Reverse Transcriptase Polymerase Chain Reaction
Stem Cells
Transcription Factors
