Disruption of the HNF-4 gene, expressed in visceral endoderm, leads to cell death in embryonic ectoderm and impaired gastrulation of mouse embryos.Expression of HNF-4, a transcription factor in the steroid hormone receptor superfamily, is detected only in the visceral endoderm of mouse embryos during gastrulation and is expressed in certain embryonic tissues from 8.5 days of gestation. To examine the role of HNF-4 during embryonic development, we disrupted the gene in embryonic stem cells and found that the homozygous loss of functional HNF-4 protein was an embryonic lethal. Cell death was evident in the embryonic ectoderm at 6.5 days when these cells normally initiate gastrulation. As assessed by expression of Brachyury and HNF-3 beta, primitive streak formation and initial differentiation of mesoderm do occur, but with a delay of approximately 24 h. Development of embryonic structures is severely impaired. These results demonstrate that the expression of HNF-4 in the visceral endoderm is essential for embryonic ectoderm survival and normal gastrulation.
Expression of transcription factor HNF-4 in the extraembryonic endoderm, gut, and nephrogenic tissue of the developing mouse embryo: HNF-4 is a marker for primary endoderm in the implanting blastocyst.Stephen A. Duncan, Katia Manova, W S Chen et al.|Proceedings of the National Academy of Sciences|1994 The expression of HNF-4 (hepatocyte nuclear factor 4) mRNA in postimplantation mouse embryos was analyzed by in situ hybridization. Expression was found in the primary endoderm at embryonic day 4.5 and was restricted to the columnar visceral endoderm cells of the yolk sac from day 5.5 to day 8.5. HNF-4 mRNA was first detected in embryonic tissues at day 8.5, in the liver diverticulum and the hindgut. At later times HNF-4 transcripts were observed in the mesonephric tubules, pancreas, stomach, and intestine and, still later, in the metanephric tubules of the developing kidney. This expression pattern suggests that HNF-4 has a role in the earliest stages of murine postimplantation development as well as in organogenesis.
The different tissue transcription patterns of genes for HNF-1, C/EBP, HNF-3, and HNF-4, protein factors that govern liver-specific transcription.Kleanthis G. Xanthopoulos, Vincent R. Prezioso, W S Chen et al.|Proceedings of the National Academy of Sciences|1991 The transcription factors that act in hepatocyte-specific gene expression include proteins that are present mainly in liver cells (HNF-1/LFB1, C/EBP, HNF-3, HNF-4) (HNF, hepatocyte nuclear factor; C/EBP, rat enhancer binding protein) and proteins that are widely distributed (AP-1, NF-1, NF-Y/ACF). We show here that the genes encoding each of these liver-enriched factors exhibit different patterns of transcriptional control in different tissues. In addition, there were several instances in which transcription was detected (e.g., for HNF-1) when no mRNA or specific DNA binding protein was found, suggesting the importance of posttranscriptional control in some instances for these factors. These experiments identify C/EBP, HNF-3, and HNF-4, and perhaps also HNF-1, as targets for the study of cascades of transcriptionally controlled transcription factors in differentiated cells.