In situ hybridization with 33P-labeled RNA probes for determination of cellular expression patterns of liver transcription factors in mouse embryos.
Murine hepatocyte nuclear factor-3beta (HNF-3beta) protein is a member of a large family of developmentally regulated transcription factors that share homology in the winged helix/fork head DNA binding domain and that participate in embryonic pattern formation. HNF-3beta also mediates cell-specific transcription of genes important for the function of hepatocytes, intestinal and bronchiolar epithelium, and pancreatic acinar cells. We have previously identified a hepatocyte and pancreatic cut-homeodomain transcription factor, HNF-6, which is required for HNF-3beta promoter activity. In this study, we used in situ hybridization studies of stage-specific embryos to demonstrate that HNF-6 and its target gene, HNF-3beta, are coexpressed in the foregut endoderm and in the pancreatic and hepatic diverticulum. More detailed analysis of HNF-6 and HNF-3beta's developmental expression patterns provides evidence of colocalization in hepatocytes, intestinal epithelium, and pancreatic ductal epithelium and exocrine acinar cells. In support of the role of HNF-6 in regulating HNF-3beta expression in developing hepatocytes, their liver expression levels are both transiently reduced between 14 and 15 days of gestation. At day 18 of gestation and in adult pancreas, HNF-6 and HNF-3beta transcripts remain colocalized in the exocrine acinar cells, but their expression patterns diverge in endocrine cells. HNF-3beta expression is restricted to the endocrine cells of the islets of Langerhans, whereas the ductal epithelium expresses HNF-6. We discuss these expression patterns with respect to specification of hepatocytes and differentiation of the endocrine and exocrine pancreas.
Rausa
F M
FM
Department of Biochemistry and Molecular Biology, University of Illinois at Chicago, College of Medicine, Chicago, Illinois, 60612-7334, USA.
Ye
H
H
Lim
L
L
Duncan
S A
SA
Costa
R H
RH
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D005865:Gestational Age; D051542:Hepatocyte Nuclear Factor 3-beta; D051559:Hepatocyte Nuclear Factor 6; D018398:Homeodomain Proteins / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D007422:Intestines / Q000196:embryology; D008099:Liver / Q000196:embryology; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000235:genetics; D010179:Pancreas / Q000196:embryology; D010759:Phosphorus Isotopes; D011228:Prealbumin / Q000235:genetics; D011401:Promoter Regions, Genetic; D015347:RNA Probes / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000032:analysis*
D004268:DNA-Binding Proteins; C496503:Foxa2 protein, mouse; D051559:Hepatocyte Nuclear Factor 6; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; C496606:Onecut1 protein, mouse; D010759:Phosphorus Isotopes; D011228:Prealbumin; D015347:RNA Probes; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D051542:Hepatocyte Nuclear Factor 3-beta