Tissue specificity of alpha-fetoprotein messenger RNA expression during mouse embryogenesis.

Dziadek, Marie; Andrews, Glen K.

doi:10.1002/j.1460-2075.1983.tb01461.x

Cited by 114 publications

(51 citation statements)

References 49 publications

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“…The actual events involved in this commitment of the mesoderm to hematopoietic cells are not known but are thought to involve interactions between mesoderm and the extraembryonic endoderm of the yolk sac, which is itself derived from the primitive endoderm (42,64). Thus, in the initial study, we analyzed the developing EBs for the presence of marker genes indicative of primitive ectoderm or ES cells (activin OiB [3]), mesoderm (Brachyury [29,62]), primitive endoderm (collagen a IV [2]), and visceral endoderm (alpha-fetoprotein [AFP] [19,20,30]) to determine whether these various cell population develop in culture.…”

Section: Methodsmentioning

confidence: 99%

Hematopoietic commitment during embryonic stem cell differentiation in culture.

et al. 1993

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We report that embryonic stem cells efficiently undergo differentiation in vitro to mesoderm and hematopoietic cells and that this in vitro system recapitulates days 6.5 to 7.5 of mouse hematopoietic development. Embryonic stem cells differentiated as embryoid bodies (EBs) develop erythroid precursors by day 4 of differentiation, and by day 6, more than 85% of EBs contain such cells. A comparative reverse transcriptase-mediated polymerase chain reaction proffle of marker genes for primitive endoderm (collagen a IV) and mesoderm (Brachyury) indicates that both cell types are present in the developing EBs as well in normal embryos prior to the onset of hematopoiesis. GATA-1, GATA-3, and vav are expressed in both the EBs and embryos just prior to and/or during the early onset of hematopoiesis, indicating that they could play a role in the early stages of hematopoietic development both in vivo and in vitro. The initial stages of hematopoietic development within the EBs occur in the absence of added growth factors and are not significantly influenced by the addition of a broad spectrum of factors, including interleukin-3 (IL-3), IL-1, IL.6, IL-11, erythropoietin, and Kit ligand. At days 10 and 14 of differentiation, EB hematopoiesis is significantly enhanced by the addition of both Kit ligand and ILH11 to the cultures. Kinetic analysis indicates that hematopoietic precursors develop within the EBs in an ordered pattern. Precursors of the primitive erythroid lineage appear first, approximately 24 h before precursors of the macrophage and definitive erythroid lineages. Bipotential neutrophil/macrophage and multilineage precursors appear next, and precursors of the mast cell lineage develop last. The kinetics of precursor development, as well as the growth factor responsiveness of these early cells, is similar to that found in the yolk sac and early fetal liver, indicating that the onset of hematopoiesis within the EBs parallels that found in the embryo.

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Section: Methodsmentioning

confidence: 99%

Hematopoietic commitment during embryonic stem cell differentiation in culture.

et al. 1993

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“…In normal development, the fetal oncoprotein AFP is synthesized primarily in the embryonic liver and yolk sac (20,21). AFP mRNA is detectable in the hepatic primordia, which form on the 10th day of the 21-day mouse gestation period (21).…”

Section: Introductionmentioning

confidence: 99%

CCAAT/Enhancer Binding Protein α Knock-in Mice Exhibit Early Liver Glycogen Storage and Reduced Susceptibility to Hepatocellular Carcinoma

Tan¹,

Hooi²,

Laban³

et al. 2005

Cancer Research

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The CCAAT/enhancer binding protein A (C/EBPA) is vital for establishing normal hepatic energy homeostasis and moderating hepatocellular growth. CEBPA loss-of-function mutations identified in acute myeloid leukemia patients support a tumor suppressor role for C/EBPA. Recent work showed reductions of C/EBPA levels in human hepatocellular carcinoma with the reductions correlating to tumor size and progression. We investigated the potential of reactivating c/ebpa expression during hepatic carcinogenesis to prevent tumor cell growth. We have developed a c/ebpa knock-in mouse in which a single-copy c/ebpa is regulated by one allele of the A-fetoprotein (AFP) gene promoter. The knock-in mice are physically indistinguishable from wild-type (WT) controls. However, knock-in animals were found to deposit fetal hepatic glycogen earlier than WT animals. Quantitative real-time PCR confirmed early c/ebpa expression and early glycogen synthase gene activation in knock-in fetuses. We then used diethylnitrosamine to induce hepatocellular carcinoma in our animals. Diethylnitrosamine produced half the number of hepatocellular nodules in knock-in mice as in WT mice. Immunohistochemistry showed reduced C/EBPA content in WT nodules whereas knock-in nodules stained strongly for C/EBPA. The p21 protein was examined because it mediates a C/EBPA growth arrest pathway. Nuclear p21 was absent in WT nodules whereas cytoplasmic p21 was abundant; knock-in nodules were positive for nuclear p21. Interestingly, only C/EBPA-positive nodules were positive for nuclear p21, suggesting that C/EBPA may be required to direct p21 to the cell nucleus to inhibit growth. Our data establish that controlled C/EBPA production can inhibit liver tumor growth in vivo. (Cancer Res 2005; 65(22): 10330-7)

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“…1), the AFP gene can also be triggered without subsequent enhancement of the albumin gene. The prime activity of AFP chromatin in prehepatocytes of the gut, or in yet earlier endodermal structures of the embryo (14), suggests that the albumin/AFP locus is triggered at the AFP end. These initial induction events are a primary target in the context of developmental and cancer biology, and whether they are directly connected with AFP gene deactivation in late development has remained a challenging question.…”

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confidence: 99%

Functional analysis of developmentally regulated chromatin-hypersensitive domains carrying the alpha 1-fetoprotein gene promoter and the albumin/alpha 1-fetoprotein intergenic enhancer.

Bernier¹,

Thomassin²,

Allard³

et al. 1993

Mol. Cell. Biol.

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During liver development, the tandem ac-fetoprotein (AFP)/albumin locus is triggered at the AFP end and then asymmetrically enhanced; this is followed by autonomous repression of the AFP-encoding gene. To understand this regulation better, we characterized the two early developmental stage-specific DNase I-hypersensitive (DH) sites so far identified in rat liver AFP/albumin chromatic: an intergenic DH-enhancer site and the AFP DH-promoter site. Mutation-transfection analyses circumscribed the DH-enhancer domain to a 200-bp DNA segment stringently conserved among species. Targeted mutations, DNA-protein-binding assays, and coexpression experiments pinpointed C/EBP as the major activator component of the intergenic enhancer.Structure-function relationships at the AFP DH-promoter site defined a discrete glucocorticoid-regulated domain activated cooperatively by HNF1 and a highly specific AFP transcription factor, F1F, which binds to a steroid receptor recognition motif. The HNF1/FTF/DNA complex is deactivated by glucocorticoid receptors or by the ubiquitous factor NF1, which eliminates HNF1 by competition at an overlapping, high-affinity binding site. We propose that the HNF1-NF1 site might serve as a developmental switch to direct autonomous AFP gene repression in late liver development. We also conclude that the intergenic enhancer is driven by C/EBPat primarily to fulfill albumin gene activation functions at early developmental stages. Factor FTF seems to be the key regulator of AFP gene-specific functions in carcinoembryonic states.

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Tissue specificity of alpha-fetoprotein messenger RNA expression during mouse embryogenesis.

Cited by 114 publications

References 49 publications

Hematopoietic commitment during embryonic stem cell differentiation in culture.

Hematopoietic commitment during embryonic stem cell differentiation in culture.

CCAAT/Enhancer Binding Protein α Knock-in Mice Exhibit Early Liver Glycogen Storage and Reduced Susceptibility to Hepatocellular Carcinoma

Functional analysis of developmentally regulated chromatin-hypersensitive domains carrying the alpha 1-fetoprotein gene promoter and the albumin/alpha 1-fetoprotein intergenic enhancer.

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