The nuclear receptor fetoprotein transcription factor is coexpressed with its target gene HNF-3β in the developing murine liver intestine and pancreas

Abstract

During organogenesis, the winged helix hepatocyte nuclear factor 3beta (HNF-3beta) protein participates in regulating gene transcription in the developing esophagus, trachea, liver, lung, pancreas, and intestine. Hepatoma cell transfection studies identified a critical HNF-3beta promoter factor, named UF2-H3beta, and here, we demonstrate that UF2-H3beta is identical to the fetoprotein transcription factor (FTF). In situ hybridization studies of mouse embryos demonstrate that FTF expression initiates in the foregut endoderm during liver and pancreatic morphogenesis (day 9) and that earlier expression of FTF is observed in the yolk sac endoderm, branchial arch and neural crest cells (day 8). Abundant FTF hybridization signals are observed throughout morphogenesis of the liver, pancreas, and intestine and its expression continues in the epithelial cells of these adult organs. In day 17 mouse embryos and adult pancreas, however, expression of FTF becomes restricted to the exocrine acinar and ductal epithelial cells.

The Fetoprotein Transcription Factor (FTF) Gene Is Essential to Embryogenesis and Cholesterol Homeostasis and Is Regulated by a DR4 Element

“…6) cloned in pBluescript SKϩ: the sense probe was obtained with HindIII-digested DNA and T7 RNA polymerase and the antisense probe with ClaIdigested DNA and T3 RNA polymerase, with radiolabeling using [␣-33 P]UTP. HNF3␤ probes were obtained as before (10). Embryos were fixed 15-20 h in 4% paraformaldehyde/PBS, dehydrated in ethanol and toluene, and embedded in paraffin.…”

“…In situ hybridization analysis in the mouse at embryonic day 8 -9 showed abundant FTF transcripts in the foregut endoderm, before liver morphogenesis (10). Characterization of the FTF gene promoter also revealed a cluster of regulatory motifs conserved in distant species and potential targets of cell lineage specification factors (11).…”

LRH-1 and PTF1-L coregulate an exocrine pancreas-specific transcriptional network for digestive function

“…LRH-1 is present during the earliest stages of development and in embryonic stem cells, where it maintains pluripotency (Pare et al 2004;Gu et al 2005;Heng et al 2010). In adults, LRH-1 is abundantly expressed in endoderm-derived enterohepatic tissues (Rausa et al 1999), where it regulates genes involved in cholesterol, fatty acid, and bile acid homeostasis, and intestinal epithelial cell renewal (Fayard et al 2004;Lee and Moore 2008). LRH-1 is also expressed in both the acinar and ductal cells of the exocrine pancreas (Rausa et al 1999).…”

“…In adults, LRH-1 is abundantly expressed in endoderm-derived enterohepatic tissues (Rausa et al 1999), where it regulates genes involved in cholesterol, fatty acid, and bile acid homeostasis, and intestinal epithelial cell renewal (Fayard et al 2004;Lee and Moore 2008). LRH-1 is also expressed in both the acinar and ductal cells of the exocrine pancreas (Rausa et al 1999). While LRH-1 regulates expression of carboxyl ester lipase in acinar cells (Fayard et al 2003), little else is known about its function in this tissue.…”

Gene expression profile in liver of hB1F transgenic mice

“…The tissue expression pattern of hB1F transgene was expected since the transcription of thet ransgene was under the control of the CMV early promoter which has a relative broad tissue expression range. Although hB1F was thought previously to be present mainly in liver and pancreas, recent data revealed that it could be expressed in many types of tissues, such as intestine [10,16] , ovary [17] , adrenal gland [12] , and preadipocytes [11,18] . Therefore, the transgenic lines established and verified in this study would provide a valuable animal model for studying the function of hB1F in multiple tissues.…”