Mammalian hepatocyte differentiation requires the transcription factor HNF-4α

Jixuan Li, Gang Ning, Stephen A. Duncan

Research output: Contribution to journalArticlepeer-review

422 Scopus citations

Abstract

HNF-4α 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-4α 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-4α toward liver development and hepatocyte differentiation. However, we have shown that complementation of HNF-4α(-/-) embryos with a tetraploid embryo-derived wild-type visceral endoderm rescues this early developmental arrest and allows HNF-4α(-/-) embryos to proceed normally through midgestation stages of development. Examination of these rescued embryos revealed that HNF-4α was dispensable for specification and early development of the liver. However, HNF-4α(-/-) 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-4α is essential for expression of the transcription factors HNF- 1α and PXR within the fetal liver. We therefore conclude that HNF-4α is both essential for hepatocyte differentiation during mammalian liver development and also crucial for metabolic regulation and liver function.

Original languageEnglish (US)
Pages (from-to)464-474
Number of pages11
JournalGenes and Development
Volume14
Issue number4
StatePublished - 2000

All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology

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