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Programmed cell death in the absence of c-Fos and c-Jun
S. Roffler-Tarlov, J.J. Brown, E. Tarlov, J. Stolarov, D.L. Chapman, M. Alexiou, V.E. Papaioannou
Development 1996 122: 1-9;

Summary

Programmed cell death, or apoptosis, is a normal process in the development of a variety of embryonic and adult tissues, and is also observed in several pathological conditions. Several recent studies, using both expression and functional assays, have implicated the transcription factor, AP-1, in the regulation of programmed cell death, and specifically implicate the genes c-fos and c-jun, as well as some other family members. If the products of the c-fos and/or c-jun genes are essential components in the cascade of events that leads to programmed cell death in mammalian cells, it follows that cell death would not occur in mice lacking functional copies of these genes. We have made use of null mutations in the c-fos and c-jun genes that were produced by gene targeting (Johnson, R.S., Spiegelman, B.M. and Papaioannou, V.E. (1992). Cell 71, 577–586; Johnson, R.S., Van Lingen, B., Papaioannou, V.E. and Spiegelman, B.M. (1993). Genes Dev. 7, 1309–1317) to investigate this possibility. Cell death was assayed using an in situ apoptosis assay in c-fos null embryos and adults, c-jun null embryos, and c-fos/c-jun double null embryos compared with control mice. The occurrence of cell death in c-fos null mice was also assessed in two experimental conditions that normally lead to neuronal cell death. The first was unilateral section of the sciatic nerve in neonates, which leads to the death of anterior horn cells of the spinal cord on the operated side. The second was a genetic cross combining the weaver mutation, which causes death of cerebellar granule cells, with the c-fos mutation. Our results show that programmed cell death occurs normally in developing embryonic tissues and adult thymus and ovary, regardless of the absence of a functional c-fos gene. Furthermore, absence of c-fos had no effect on neuronal cell death in the spinal cord following sciatic nerve section, or in heterozygous weavers' cerebellae. Finally, the results show that programmed cell death can take place in embryos lacking both Fos and Jun.

Reference

    1. Buttyan R.,
    2. Olsson C. A.,
    3. Pintar J.,
    4. Chang C.,
    5. Bandyk M.,
    6. Ng P.-Y.,
    7. Sawczuk I. S.
    (1989) Induction of the TRPM-2 gene in cells undergoing programmed death. Mol.Cell Biol 9, 3473–3481
    OpenUrlAbstract/FREE Full Text
    1. Buttyan R.,
    2. Zakeri Z.,
    3. Lockshin R.,
    4. Wolgemuth D.
    (1988) Cascade induction of c- fos, c- myc and heat shock 70K transcripts during regression of the rat ventral prostate gland. Mol. Endocrinol 2, 650–657
    OpenUrlCrossRefPubMedWeb of Science
    1. Colotta F.,
    2. Polentarutti N.,
    3. Sironi M.,
    4. Mantovani A.
    (1992) Expression and involvement of c- fos and c -jun protooncogenes in programmed cell death induced by growth factor deprivation in lymphoid cell lines. J. Biol. Chem 267, 18278–18283
    OpenUrlAbstract/FREE Full Text
    1. Driscoll M.,
    2. Chalfie M.
    (1992) Developmental and abnormal cell death in C. elegans. Trends Neurosci 15, 15–19
    OpenUrlCrossRefPubMedWeb of Science
    1. Ellis R. E.,
    2. Yuan J.,
    3. Horwitz H. R.
    (1991) Mechanisms and functions of cell death. Annu. Rev. Cell Biol 7, 663–698
    OpenUrlCrossRefWeb of Science
    1. Estus S.,
    2. Zaks W. J.,
    3. Freeman R. S.,
    4. Gruda M.,
    5. Bravo R.,
    6. Johnson E. M., Jr
    (1994) Altered gene expression in neurons during programmed cell death: Identification of c -jun as necessary for neuronal apoptosis. J. Cell Biol 127, 1717–1727
    OpenUrlAbstract/FREE Full Text
    1. Evan G. I.,
    2. Wyllie A. H.,
    3. Gilbert C. S.,
    4. Littlewood T. D.,
    5. Land H.,
    6. Brooks M.,
    7. Waters C. M.,
    8. Penn L. Z.,
    9. Hancock D. C.
    (1992) Induction of apoptosis in fibroblasts by c- myc protein. Cell 69, 119–128
    OpenUrlCrossRefPubMedWeb of Science
    1. Gagliardini V.,
    2. Fernandez P.,
    3. Lee R. K. K.,
    4. Drexler H. C. A.,
    5. Rotello R. J.,
    6. Fishman M. C.,
    7. Yuan J.
    (1994) Prevention of vertebrate neuronal death by the crmA gene. Science 263, 826–828
    OpenUrlAbstract/FREE Full Text
    1. Gavrieli Y.,
    2. Sherman Y.,
    3. Ben-Sasson S. A.
    (1992) Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J. Cell Biol 119, 493–501
    OpenUrlAbstract/FREE Full Text
    1. Gillardon F.,
    2. Eschenfelder C.,
    3. Uhhlmann E.,
    4. Hartschuh W.,
    5. Zimmermann M.
    (1994) Differential regulation of c- fos, fosB, c- jun, junB, bcl-2 and bax expression in rat skin following single or chronic ultraviolet radiation and in vivo modulation by antisense oligodeoxynucleotide superfusion. Oncogene 9, 3219–3225
    OpenUrlPubMedWeb of Science
    1. Glucksmann A.
    (1951) Cell deaths in normal vertebrate ontogeny. Biol. Rev. Cambridge Philos. Soc 26, 59–86
    OpenUrlCrossRef
    1. Gonzales-Martin C.,
    2. De Diego I.,
    3. Crespo D.,
    4. Fairen A.
    (1992) Transient c- fos expression accompanies naturally occurring cell death in the developing interhemispheric cortex of the rat. Dev. Brain Res 68, 83–95
    OpenUrlCrossRefPubMed
    1. Grassilli E.,
    2. De Prati A. C.,
    3. Monti K.,
    4. Troiano L.,
    5. Menegazzi M.,
    6. Barbieri D.,
    7. Franceschi C.,
    8. Suzuki H.
    (1992) Studies of the relationship between cell proliferation and cell death. II. Early gene expression during concanavalin A-induced proliferation or dexamethasone-induced apoptosis of rat thymocytes. Biochem. Biophys. Res. Comm 188, 1261–1266
    OpenUrlCrossRefPubMed
    1. Grigoriadis A. E.,
    2. Wang Z.-Q.,
    3. Cecchini M. G.,
    4. Hofstetter W.,
    5. Felix R.,
    6. Fleisch H. A.,
    7. Wagner E. F.
    (1994) c- Fos: a key regulator of osteoclast-macrophage lineage determination and bone remodelling. Science 266, 443–448
    OpenUrlAbstract/FREE Full Text
    1. Ham J.,
    2. Babij C.,
    3. Whitfield J.,
    4. Pharr C. M.,
    5. Lallemand D.,
    6. Yaniv M.
    (1995) A c- Jun dominant negative mutant protects sympathetic neurons against programmed cell death. Neuron 14, 927–939
    OpenUrlCrossRefPubMedWeb of Science
    1. Hamburger V.,
    2. Levi-Montalcini R.
    (1949) Proliferation, differentiation and degeneration in the spinal ganglia of the chick embryo under normal and experimental conditions. J. Exp. Zool 111, 457–502
    OpenUrlCrossRefPubMedWeb of Science
    1. Harrison S. M. W.,
    2. Roffler-Tarlov S.
    (1994) Male-sterile phenotype of the neurological mouse mutant weaver. Dev. Dynamics 200, 26–38
    OpenUrlPubMedWeb of Science
    1. Hengartner M. O.,
    2. Ellis R. E.,
    3. Horvitz H. R.
    (1992) Caenorhabditis elegans gene ced-9 protects cells from programmed cell death. Nature 356, 494–499
    OpenUrlCrossRefPubMed
    1. Hilberg F.,
    2. Aguzzi A.,
    3. Howells N.,
    4. Wagner E. F.
    (1993) c- Jun is essential for normal mouse development and hepatogenesis. Nature 365, 179–181
    OpenUrlCrossRefPubMed
    1. Johnson D. R.
    (1969) Polysyndactyly, a new mutant gene in the mouse. J. Embryol. exp. Morph 21, 285–295
    OpenUrlPubMed
    1. Johnson R. S.,
    2. Spiegelman B. M.,
    3. Papaioannou V. E.
    (1992) Pleiotropic effects of a null mutation in the c- fos proto-oncogene. Cell 71, 577–586
    OpenUrlCrossRefPubMedWeb of Science
    1. Johnson R. S.,
    2. Van Lingen B.,
    3. Papaioannou V. E.,
    4. Spiegelman B. M.
    (1993) Effects of a mutation at the c- jun proto-oncogene. Genes Dev 7, 1309–1317
    OpenUrlAbstract/FREE Full Text
    1. Luciano A. M.,
    2. Pappalardo A.,
    3. Ray C.,
    4. Peluso J. J.
    (1994) Epidermal growth factor inhibits large granulosa cell apoptosis by stimulating progesterone synthesis and regulating the distribution of intracellular free calcium. Biol. Reprod 51, 646–654
    OpenUrlAbstract
    1. Marti A.,
    2. Jehn B.,
    3. Costello E.,
    4. Keon N.,
    5. Ke G.,
    6. Martin F.,
    7. Jaggi R.
    (1994) Protein kinase A and AP-1 (c-Fos/JunD) are induced during apoptosis of mouse mammary epithelial cells. Oncogene 9, 1213–1223
    OpenUrlPubMedWeb of Science
    1. Mori C.,
    2. Nakamura N.,
    3. Okamoto Y.,
    4. Osawa M.,
    5. Shiota K.
    (1994) Cytochemical identification of programmed cell death in the fusing fetal mouse palate by specific labelling of DNA fragmentation. Anat. Embryol 190, 21–28
    OpenUrlPubMed
    1. Oppenheim R. W.
    (1989) The neurotrophic theory and naturally occurring motoneuron death. Trends Neurosci 12, 252–255
    OpenUrlCrossRefPubMedWeb of Science
    1. Oppenheim R. W.
    (1991) Cell death during development of the nervous system. Annu. Rev. Neurosci 14, 453–501
    OpenUrlCrossRefPubMedWeb of Science
    1. Pexieder T.
    (1975) Cell death in the morphogenesis and teratogenesis of the heart. Adv. Anat. Embryol. Cell Biol 51, 1–100
    OpenUrlPubMed
    1. Piacentini M.,
    2. Autuori F.
    (1994) Immunohistochemical localization of tissue transglutaminase and bcl-2 in rat uterine tissues during embryo implantation and post-partum involution. Differen 57, 51–61
    OpenUrlCrossRefPubMed
    1. Rakic P.,
    2. Sidman R. L.
    (1973) Sequence of developmental abnormalities leading to granule cell deficit in cerebellar cortex of weaver mutant mice. J. Comp. Neurol 152, 103–132
    OpenUrlCrossRefPubMedWeb of Science
    1. Raff M. C.
    (1992) Social controls on cell survival and cell death. Nature 256, 397–400
    OpenUrl
    1. Rezai Z.,
    2. Yoon C. H.
    (1972) Abnormal rate of granule cell migration in the cerebellum of ‘ weaver ‘ mutant mice. Dev. Biol 29, 17–26
    OpenUrlCrossRefPubMedWeb of Science
    1. Roffler-Tarlov S.,
    2. Cheng S.,
    3. Lin C. S.,
    4. Wensley C. H.,
    5. Grabiel A. M.,
    6. Gusella J. F.
    (1994) The chromosomal location of the murine mutation weaver. Neurodegeneration 3, 61–72
    OpenUrl
    1. Sikora E.,
    2. Grassilli E.,
    3. Radziszewska E.,
    4. Bellesia E.,
    5. Barbieri D.,
    6. Franceschi C.
    (1993) Transcription factors DNA-binding activity in rat thymocytes undergoing apoptosis after heat-shock or dexamethasone treatment. Biochem. Biophys. Res. Comm 197, 709–715
    OpenUrlCrossRefPubMedWeb of Science
    1. Smeyne R. J.,
    2. Vendrell M.,
    3. Hayward M.,
    4. Baker S. J.,
    5. Miao G. G.,
    6. Schilling K.,
    7. Robertson L. M.,
    8. Curran T.,
    9. Morgan J. I.
    (1993) Continuous c- fos expression precedes programmed cell death in vivo. Nature 363, 166–169
    OpenUrlCrossRefPubMed
    1. Surh C. D.,
    2. Sprent J.
    (1994) T-cell apoptosis detected in situ during positive and negative selection in the thymus. Nature 372, 100–103
    OpenUrlCrossRefPubMedWeb of Science
    1. van der Hoven F.,
    2. Schimmang T.,
    3. Volkmann A.,
    4. Mattei M.-G.,
    5. Kyewski B.,
    6. Ruther U.
    (1994) Programmed cell death is affected in the novel mouse mutant Fused toes (Ft). Development 120, 2601–2607
    OpenUrlAbstract/FREE Full Text
    1. Veis D. J.,
    2. Sorenson C.,
    3. Shutter J. R.,
    4. Korsmeyer S. J.
    (1993) Bcl-2 deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys and hypopigmented hair. Cell 75, 229–240
    OpenUrlCrossRefPubMedWeb of Science
    1. Walker P. R.,
    2. Kwast-Welfeld J.,
    3. Gourdeau H.,
    4. Leblanc J.,
    5. Neugebauer W.,
    6. Sikorska M.
    (1993) Relationship between apoptosis and the cell cycle in lymphocytes: roles of protein kinase C, tyrosine phosphorylation, and AP-1. Exp. Cell Res 207, 142–151
    OpenUrlCrossRefPubMedWeb of Science
    1. Wang Z.-Q.,
    2. Ovitt C.,
    3. Grigoriadis A. E.,
    4. Mohle-Steinlein U.,
    5. Ruther U.,
    6. Wagner E. F.
    (1992) Bone and haematopoietic defects in mice lacking c- fos. Nature 360, 741–745
    OpenUrlCrossRefPubMedWeb of Science
    1. Williams G. T.,
    2. Smith C. A.,
    3. Spooncer E.,
    4. Dexter T. M.,
    5. Taylor D. R.
    (1990) Haemopoietic colony stimulating factors promote cell survival by suppressing apoptosis. Nature 343, 76–79
    OpenUrlCrossRefPubMed
    1. Yonish-Rouach E.,
    2. Resnitzky D.,
    3. Lotem J.,
    4. Sachs L.,
    5. Kimchi A.,
    6. Oren M.
    (1991) Wild-type p53 induces apoptosis of myeloid leukemic cells that is inhibited by interleukin-6. Nature 352, 345–347
    OpenUrlCrossRefPubMedWeb of Science
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JOURNAL ARTICLES
Programmed cell death in the absence of c-Fos and c-Jun
S. Roffler-Tarlov, J.J. Brown, E. Tarlov, J. Stolarov, D.L. Chapman, M. Alexiou, V.E. Papaioannou
Development 1996 122: 1-9;
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