DOI: 10.1083/jcb.145.5.1049. Functions of c-Jun in Liver and Heart Development

Functions of c-Jun in Liver and Heart Development

10.1083/jcb.145.5.1049

Crossref journal-article

Rockefeller University Press

The Journal of Cell Biology (291)

Abstract

Mice lacking the AP-1 transcription factor c-Jun die around embryonic day E13.0 but little is known about the cell types affected as well as the cause of embryonic lethality. Here we show that a fraction of mutant E13.0 fetal livers exhibits extensive apoptosis of both hematopoietic cells and hepatoblasts, whereas the expression of 15 mRNAs, including those of albumin, keratin 18, hepatocyte nuclear factor 1, β-globin, and erythropoietin, some of which are putative AP-1 target genes, is not affected. Apoptosis of hematopoietic cells in mutant livers is most likely not due to a cell-autonomous defect, since c-jun−/− fetal liver cells are able to reconstitute all hematopoietic compartments of lethally irradiated recipient mice. A developmental analysis of chimeras showed contribution of c-jun−/− ES cell derivatives to fetal, but not to adult livers, suggesting a role of c-Jun in hepatocyte turnover. This is in agreement with the reduced mitotic and increased apoptotic rates found in primary liver cell cultures derived from c-jun−/− fetuses. Furthermore, a novel function for c-Jun was found in heart development. The heart outflow tract of c-jun−/− fetuses show malformations that resemble the human disease of a truncus arteriosus persistens. Therefore, the lethality of c-jun mutant fetuses is most likely due to pleiotropic defects reflecting the diversity of functions of c-Jun in development, such as a role in neural crest cell function, in the maintenance of hepatic hematopoiesis and in the regulation of apoptosis.

Bibliography

Eferl, R., Sibilia, M., Hilberg, F., Fuchsbichler, A., Kufferath, I., Guertl, B., Zenz, R., Wagner, E. F., & Zatloukal, K. (1999). Functions of c-Jun in Liver and Heart Development. The Journal of Cell Biology, 145(5), 1049â1061.

Authors 9

Robert Eferl (first)
Maria Sibilia (additional)
Frank Hilberg (additional)
Andrea Fuchsbichler (additional)
Iris Kufferath (additional)
Barbara Guertl (additional)
Rainer Zenz (additional)
Erwin F. Wagner (additional)
Kurt Zatloukal (additional)

References 55 Referenced 235

{'key': '2023072900384033800_B1', 'first-page': '2256', 'article-title': '12-O-tetradecanoyl-phorbol-13-acetate induction of the human collagenase gene is mediated by an inducible enhancer element located in the 5′-flanking region', 'volume': '7', 'author': 'Angel', 'year': '1987', 'journal-title': 'Mol Cell Biol'} / Mol Cell Biol / 12-O-tetradecanoyl-phorbol-13-acetate induction of the human collagenase gene is mediated by an inducible enhancer element located in the 5′-flanking region by Angel (1987)
10.1038/6854 / Nat Genet / Amino-terminal phosphorylation of c-Jun regulates stress-induced apoptosis and cellular proliferation by Behrens (1999)
10.1016/0092-8674(92)90187-H / Cell / Functional antagonism between c-Jun and MyoD proteins: a direct physical association by Bengal (1992)
10.1093/emboj/16.7.1695 / EMBO (Eur Mol Biol Organ) J / Induction of apoptosis by the transcription factor c-Jun by Bossy-Wetzel (1997)
10.1016/S0008-6363(97)00172-7 / Cardiovasc Res / Development of a lethal congenital heart defect in the splotch (pax3) mutant mouse by Conway (1997)
10.1016/S0025-6196(11)63624-0 / Mayo Clin Proc / Ludwig symposium on biliary disorders part I: pathogenesis of ductal plate abnormalities by Desmet (1998)
10.1016/S0168-9525(00)89107-6 / Trends Genet / Mouse embryonic hematopoiesis by Dzierzak (1995)
10.1159/000128339 / Eur Surg Res / Isolation of mouse liver cells: perfusion technique and metabolic evaluation by Edström (1983)
{'key': '2023072900384033800_B9'}
10.1083/jcb.127.6.1717 / J Cell Biol / Altered gene expression in neurons during programmed cell death: identification of c-junas necessary for neuronal apoptosis by Estus (1994)
10.1016/0092-8674(90)90422-B / Cell / Activation of the ovalbumin gene by estrogen receptor involves the fos-jun complex by Gaub (1990)
10.1126/science.7939685 / Science / C-Fos: a key regulator of osteoclast-macrophage lineage determination and bone remodeling by Grigoriadis (1994)
10.1016/0896-6273(95)90331-3 / Neuron / A c-jundominant negative mutant protects sympathetic neurons against programmed cell death by Ham (1995)
10.1038/365179a0 / Nature / c-Jun is essential for normal mouse development and hepatogenesis by Hilberg (1993)
10.1016/0092-8674(92)90592-Z / Cell / Pleiotropic effects of a null mutation in the c-fos proto-oncogene by Johnson (1992)
10.1101/gad.7.7b.1309 / Genes Dev / A null mutation at the c-junlocus causes embryonic lethality and retarded cell growth in culture by Johnson (1993)
10.1016/0092-8674(90)90395-U / Cell / Antitumor promotion and antiinflamation: down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone by Jonat (1990)
10.1126/science.2462278 / Science / Growth factors regulate transin gene expression by c-fos-dependent and c-fos-independent pathways by Kerr (1988)
10.1161/01.CIR.82.2.332 / Circulation / Role of neural crest in congenital heart disease by Kirby (1990)
10.1161/01.RES.77.2.211 / Circ Res / Neural crest and cardiovascular patterning by Kirby (1995)
10.1172/JCI113564 / J Clin Invest / Erythropoietin messenger RNA levels in developing mice and transfer of 125I-erythropoietin by the placenta by Koury (1988)
10.1016/0003-2697(83)90299-3 / Anal Biochem / The simultaneous extraction of high-molecular-weight DNA and of RNA from solid tumors by Krieg (1983)
10.1073/pnas.87.24.9838 / Proc Natl Acad Sci USA / Molecular cloning, functional expression, and chromosomal localization of mouse hepatocyte nuclear factor 1 by Kuo (1990)
10.1093/nar/20.2.343 / Nucleic Acids Res / Structure and mapping of the fosB gene. FosB downregulates the activity of the fosB promoter by Lazo (1992)
10.1016/0092-8674(87)90612-X / Cell / Purified transcription factor AP-1 interacts with TPA-inducible enhancer elements by Lee (1987)
10.1016/0167-4781(93)90159-B / Biochim Biophys Acta / Molecular cloning and characterization of cDNA encoding mouse hepatocyte growth factor by Liu (1993)
10.1016/0092-8674(91)90101-4 / Cell / Colony-stimulating factor 1 regulates novel cyclins during the G1 phase of the cell cycle by Matsushime (1991)
{'key': '2023072900384033800_B28', 'first-page': '347', 'article-title': 'The rate of molecular evolution of alpha-fetoprotein approaches that of pseudogenes', 'volume': '2', 'author': 'Minghetti', 'year': '1985', 'journal-title': 'Mol Biol Evol'} / Mol Biol Evol / The rate of molecular evolution of alpha-fetoprotein approaches that of pseudogenes by Minghetti (1985)
10.1016/0006-291X(88)90223-9 / Biochem Res Commun / Isolation of EndoA cDNA from mouse 8-cell stage embryo by Morita (1988)
10.1101/gad.4.6.993 / Genes Dev / Tandem AP-1 binding sites within the human beta-globin dominant control region function as an inducible enhancer in erythroid cells by Ney (1990)
10.1161/01.CIR.75.1.255 / Circulation / Pathogenesis of persistent truncus arteriosus and dextroposed aorta in the chick embryo after neural crest ablation by Nishibatake (1987)
10.1126/science.272.5262.671 / Science / Molecular pathways controlling heart development by Olson (1996)
10.1101/gad.4.5.835 / Genes Dev / Activation of an intron enhancer within the keratin 18 gene by expression of c-fos and c-junin undifferentiated F9 embryonal carcinoma cells by Oshima (1990)
{'key': '2023072900384033800_B34'}
10.1242/dev.122.1.1 / Development / Programmed cell death in the absence of cFos and c-Jun by Roffler-Tarlov (1996)
10.1161/01.RES.78.3.349 / Circ Res / Mouse mutants and cardiac development: new molecular insights into cardiogenesis by Rossant (1996)
10.1016/0092-8674(90)90200-X / Cell / Two genetically defined trans-acting loci coordinately regulate overlapping sets of liver-specific genes by Ruppert (1990)
10.1073/pnas.85.22.8464 / Proc Natl Acad Sci USA / Induction of proto-oncogene c-junby serum growth factors by Ryder (1988)
10.1073/pnas.85.5.1487 / Proc Natl Acad Sci USA / A gene activated by growth factors is related to the oncogene v-jun by Ryder (1988)
10.1073/pnas.86.5.1500 / Proc Natl Acad Sci USA / junD: A third member of the jun gene family by Ryder (1989)
10.1016/0378-1119(90)90087-8 / Gene / Glyceraldehyde-3-phosphate dehydrogenase mRNA is a major interleukin 2-induced transcript in a cloned T-helper lymphocyte by Sabath (1990)
10.1093/emboj/18.4.934 / EMBO (Eur Mol Biol Organ) J / JunB is essential for mammalian placentation by Schorpp-Kistner (1999)
10.1101/gad.13.5.607 / Genes Dev / Control of cell cycle progression by c-Jun is p53-dependent by Schreiber (1999)
10.1016/0092-8674(90)90531-I / Cell / Jun/Fos and receptors for vitamin A and D recognize a common response element in the human osteocalcin gene by Schüle (1990)
10.1016/S0091-679X(08)61797-5 / Methods Cell Biol / Preparation of isolated rat liver cells by Seglen (1976)
10.1016/0022-2836(89)90363-X / J Mol Biol / Nucleotide sequence of the BALB/c mouse beta-globin complex by Shehee (1989)
{'key': '2023072900384033800_B47', 'first-page': '849', 'article-title': 'Murine erythropoietin gene: cloning, expression, and human gene homology', 'volume': '6', 'author': 'Shoemaker', 'year': '1986', 'journal-title': 'Mol Cell Biol'} / Mol Cell Biol / Murine erythropoietin gene: cloning, expression, and human gene homology by Shoemaker (1986)
10.1126/science.7618085 / Science / Strain-dependent epithelial defects in mice lacking the EGF receptor by Sibilia (1995)
10.1093/emboj/17.3.719 / EMBO (Eur Mol Biol Organ) J / A strain-independent postnatal degeneration in mice lacking the EGF receptor by Sibilia (1998)
10.1016/S0021-9258(17)36125-2 / J Biol Chem / Molecular cloning and characterisation of the EndoB cytokeratin expressed in implanted mouse embryos by Singer (1986)
10.1038/310423a0 / Nature / Nucleotide sequence comparison of normal and translocated murine c-myc genes by Stanton (1984)
10.1016/0092-8674(83)90306-9 / Cell / Analysis of FBJ-MuSV provirus and c-fos (mouse) gene reveals that viral and cellular fos gene products have different carboxy termini by van Beveren (1983)
10.1038/360741a0 / Nature / Bone and haematopoietic defects in mice lacking c-fos by Wang (1992)
10.1016/0092-8674(95)90234-1 / Cell / Generation of committed erythroid BFU-E and CFU-E progenitors does not require erythropoietin or the erythropoietin receptor by Wu (1995)
{'key': '2023072900384033800_B55', 'first-page': '427', 'article-title': 'High molecular weight component of mallory bodies detected by a monoclonal antibody', 'volume': '62', 'author': 'Zatloukal', 'year': '1990', 'journal-title': 'Lab Invest'} / Lab Invest / High molecular weight component of mallory bodies detected by a monoclonal antibody by Zatloukal (1990)

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:45 p.m.)
Deposited	2 years, 1 month ago (July 28, 2023, 8:39 p.m.)
Indexed	2 days ago (Aug. 30, 2025, 1:14 p.m.)
Issued	26 years, 3 months ago (May 31, 1999)
Published	26 years, 3 months ago (May 31, 1999)
Published Online	26 years, 3 months ago (May 31, 1999)
Published Print	26 years, 3 months ago (May 31, 1999)

Funders 0

None

BibTeX

@article{Eferl_1999, title={Functions of c-Jun in Liver and Heart Development}, volume={145}, ISSN={1540-8140}, url={http://dx.doi.org/10.1083/jcb.145.5.1049}, DOI={10.1083/jcb.145.5.1049}, number={5}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Eferl, Robert and Sibilia, Maria and Hilberg, Frank and Fuchsbichler, Andrea and Kufferath, Iris and Guertl, Barbara and Zenz, Rainer and Wagner, Erwin F. and Zatloukal, Kurt}, year={1999}, month=may, pages={1049–1061} }

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  "abstract": "<jats:p>Mice lacking the AP-1 transcription factor c-Jun die around embryonic day E13.0 but little is known about the cell types affected as well as the cause of embryonic lethality. Here we show that a fraction of mutant E13.0 fetal livers exhibits extensive apoptosis of both hematopoietic cells and hepatoblasts, whereas the expression of 15 mRNAs, including those of albumin, keratin 18, hepatocyte nuclear factor 1, \u03b2-globin, and erythropoietin, some of which are putative AP-1 target genes, is not affected. Apoptosis of hematopoietic cells in mutant livers is most likely not due to a cell-autonomous defect, since c-jun\u2212/\u2212 fetal liver cells are able to reconstitute all hematopoietic compartments of lethally irradiated recipient mice. A developmental analysis of chimeras showed contribution of c-jun\u2212/\u2212 ES cell derivatives to fetal, but not to adult livers, suggesting a role of c-Jun in hepatocyte turnover. This is in agreement with the reduced mitotic and increased apoptotic rates found in primary liver cell cultures derived from c-jun\u2212/\u2212 fetuses. Furthermore, a novel function for c-Jun was found in heart development. The heart outflow tract of c-jun\u2212/\u2212 fetuses show malformations that resemble the human disease of a truncus arteriosus persistens. Therefore, the lethality of c-jun mutant fetuses is most likely due to pleiotropic defects reflecting the diversity of functions of c-Jun in development, such as a role in neural crest cell function, in the maintenance of hepatic hematopoiesis and in the regulation of apoptosis.</jats:p>",
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      "volume": "20",
      "author": "Lazo",
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      "author": "Liu",
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      "author": "Matsushime",
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      "article-title": "The rate of molecular evolution of alpha-fetoprotein approaches that of pseudogenes",
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      "author": "Minghetti",
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      "author": "Morita",
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      "article-title": "Tandem AP-1 binding sites within the human beta-globin dominant control region function as an inducible enhancer in erythroid cells",
      "volume": "4",
      "author": "Ney",
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      "journal-title": "Genes Dev"
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      "volume": "75",
      "author": "Nishibatake",
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      "author": "Olson",
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      "author": "Sch\u00fcle",
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      "author": "Seglen",
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      "journal-title": "Methods Cell Biol"
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      "author": "Shehee",
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