| First Author | Li J | Year | 2000 |
| Journal | Genes Dev | Volume | 14 |
| Issue | 4 | Pages | 464-74 |
| PubMed ID | 10691738 | Mgi Jnum | J:60769 |
| Mgi Id | MGI:1353880 | Doi | 10.1101/gad.14.4.464 |
| Citation | Li J, et al. (2000) Mammalian hepatocyte differentiation requires the transcription factor HNF-4alpha. Genes Dev 14(4):464-74 |
| abstractText | 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. |
