Advertisement
JOURNAL ARTICLES
Steroid regulated programmed cell death during Drosophila metamorphosis
C. Jiang, E.H. Baehrecke, C.S. Thummel
Development 1997 124: 4673-4683;

Summary

During insect metamorphosis, pulses of the steroid hormone 20-hydroxyecdysone (ecdysone) direct the destruction of obsolete larval tissues and their replacement by tissues and structures that form the adult fly. We show here that larval midgut and salivary gland histolysis are stage-specific steroid-triggered programmed cell death responses. Dying larval midgut and salivary gland cell nuclei become permeable to the vital dye acridine orange and their DNA undergoes fragmentation, indicative of apoptosis. Furthermore, the histolysis of these tissues can be inhibited by ectopic expression of the baculovirus anti-apoptotic protein p35, implicating a role for caspases in the death response. Coordinate stage-specific induction of the Drosophila death genes reaper (rpr) and head involution defective (hid) immediately precedes the destruction of the larval midgut and salivary gland. In addition, the diap2 anti-cell death gene is repressed in larval salivary glands as rpr and hid are induced, suggesting that the death of this tissue is under both positive and negative regulation. Finally, diap2 is repressed by ecdysone in cultured salivary glands under the same conditions that induce rpr expression and trigger programmed cell death. These studies indicate that ecdysone directs the death of larval tissues via the precise stage- and tissue-specific regulation of key death effector genes.

REFERENCES

    1. Abbott M. K.,
    2. Lengyel J. A.
    (1991) Embryonic head involution and rotation of male terminalia require the Drosophila locus head involution defective. Genetics 129, 783–789
    OpenUrlAbstract/FREE Full Text
    1. Abrams J. M.,
    2. White K.,
    3. Fessler L. I.,
    4. Steller H.
    (1993) Programmed cell death during Drosophila embryogenesis. Development 117, 29–43
    OpenUrlAbstract/FREE Full Text
    1. Ashburner M.
    (1972) Patterns of puffing activity in the salivary gland chromosomes of Drosophila. VI. Induction by ecdysone in salivary glands of D. melanogaster cultured in vitro. Chromosoma 38, 255–281
    OpenUrlCrossRefPubMedWeb of Science
    1. Ashburner M.,
    2. Chihara C.,
    3. Meltzer P.,
    4. Richards G.
    (1974) Temporal control of puffing activity in polytene chromosomes. Cold Spring Harbor Symp. Quant. Biol 38, 655–662
    OpenUrlAbstract/FREE Full Text
    1. Baehrecke E. H.,
    2. Thummel C. S.
    (1995) The Drosophila E93 gene from the 93F early puff displays stage-and tissue-specific regulation by 20-hydroxyecdysone. Dev. Biol 171, 85–97
    OpenUrlCrossRefPubMedWeb of Science
    1. Bayer C. A.,
    2. Holley B.,
    3. Fristrom J. W.
    (1996) A switch in Broad-Complex zinc-finger isoform expression is regulated posttranscriptionally during the metamorphosis of Drosophila imaginal discs. Dev. Biol 177, 1–14
    OpenUrlCrossRefPubMedWeb of Science
    1. Berreur P.,
    2. Porcheron P.,
    3. Moriniere M.,
    4. Berreur-Bonnenfant J.,
    5. Belinski-Deutsch S.,
    6. Busson D.,
    7. Lamour-Audit C.
    (1984) Ecdysteroids during the third larval instar in l(3)ecd-1ts, a temperature-sensitive mutant of Drosophila melanogaster. Gen. Comp. Endocrin 54, 76–84
    OpenUrlCrossRefPubMedWeb of Science
    1. Birnbaum M. J.,
    2. Clem R. J.,
    3. Miller L. K.
    (1994) An apoptosis-inhibiting gene from a nuclear polyhedrosis virus encoding a peptide with Cys/His sequence motifs. J. Virol 68, 2521–2528
    OpenUrlAbstract/FREE Full Text
    1. Boyd M.,
    2. Ashburner M.
    (1977) The hormonal control of salivary gland secretion in Drosophila melanogaster: Studies in vitro. J. Insect Physiol 23, 517–523
    OpenUrlCrossRef
    1. Brand A. H.,
    2. Perrimon N.
    (1993) Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118, 401–415
    OpenUrlAbstract
    1. Brown D. D.,
    2. Wang Z.,
    3. Furlow J. D.,
    4. Kanamori A.,
    5. Schwartzman R. A.,
    6. Remo B. F.,
    7. Pinder A.
    (1996) The thyroid hormone-induced tail resorption program during Xenopus laevis metamorphosis. Proc. Natl. Acad. Sci. USA 93, 1924–1929
    OpenUrlAbstract/FREE Full Text
    1. Bump N. J.,
    2. Hackett M.,
    3. Hugunin M.,
    4. Seshagiri S.,
    5. Brady K.,
    6. Chen P.,
    7. Ferenz C.,
    8. Franklin S.,
    9. Ghayur T.,
    10. Li P.,
    11. Licari P.,
    12. Mankovich J.,
    13. Shi L.,
    14. Greenberg A. H.,
    15. Miller L. K.,
    16. Wong W. W.
    (1995) Inhibition of ICE family proteases by baculovirus antiapoptotic protein p35. Science 269, 1885–1888
    OpenUrlAbstract/FREE Full Text
    1. Cagan R. L.,
    2. Ready D. F.
    (1989) The emergence of order in the Drosophila pupal retina. Dev. Biol 136, 346–362
    OpenUrlCrossRefPubMedWeb of Science
    1. Chen P.,
    2. Nordstrom W.,
    3. Gish B.,
    4. Abrams J. M.
    (1996) grim, a novel cell death gene in Drosophila. Genes Dev 10, 1773–1782
    OpenUrlAbstract/FREE Full Text
    1. Cleveland J. L.,
    2. Ihle J. N.
    (1995) Contenders in FasL/TNF Death Signaling. Cell 81, 479–482
    OpenUrlCrossRefPubMedWeb of Science
    1. Crook N. E.,
    2. Clem R. J.,
    3. Miller L. K.
    (1993) An apoptosis-inhibiting baculovirus gene with a zinc finger-like motif. J. Virol 67, 2168–2174
    OpenUrlAbstract/FREE Full Text
    1. Crossgrove K.,
    2. Bayer C. A.,
    3. Fristrom J. W.,
    4. Guild G. M.
    (1996) The Drosophila Broad-Complex early gene directly regulates late gene transcription during the ecdysone-induced puffing cascade. Dev. Biol 180, 745–758
    OpenUrlCrossRefPubMedWeb of Science
    1. Deveraux Q. L.,
    2. Takahashi R.,
    3. Salvesen G. S.,
    4. Reed J. C.
    (1997) X-linked IAP is a direct inhibitor of cell-death proteases. Nature 388, 300–304
    OpenUrlCrossRefPubMedWeb of Science
    1. DiBello P. R.,
    2. Withers D. A.,
    3. Bayer C. A.,
    4. Fristrom J. W.,
    5. Guild G. M.
    (1991) The Drosophila Broad-Complex encodes a family of related proteins containing zinc fingers. Genetics 129, 385–397
    OpenUrlAbstract/FREE Full Text
    1. Dieken E. S.,
    2. Miesfeld R. L.
    (1992) Transcriptional transactivation functions localized to the glucocorticoid receptor N terminus are necessary for steroid induction of lymphocyte apoptosis. Mol. Cell. Biol 12, 589–597
    OpenUrlAbstract/FREE Full Text
    1. Dominick O. S.,
    2. Truman J. W.
    (1985). The physiology of wandering behavior in Manduca sexta. II. The endocrine control of wandering behavior. J. Exp. Biol 117, 45–68
    OpenUrlAbstract/FREE Full Text
    1. Duckett C. S.,
    2. Nava V. E.,
    3. Gedrich R. W.,
    4. Clem R. J.,
    5. Van Dongen J. L.,
    6. Gilfillan M. C.,
    7. Shiels H.,
    8. Hardwick J. M.,
    9. Thompson C. B.
    (1996) A conserved family of cellular genes related to the baculovirus iap gene and encoding apoptosis inhibitors. EMBO J 15, 2685–2694
    OpenUrlPubMedWeb of Science
    1. Emery I. F.,
    2. Bedian V.,
    3. Guild G. M.
    (1994) Differential expression of Broad-Complex transcription factors may forecast tissue-specific developmental fates during Drosophila metamorphosis. Development 120, 3275–3287
    OpenUrlAbstract
    1. Evans-Storms R. B.,
    2. Cidlowski J. A.
    (1995) Regulation of apoptosis by steroid hormones. J. Steroid Biochem. Mol. Biol 53, 1–6
    1. Finlayson L. H.
    (1956) Normal and induced degeneration of abdominal muscles during metamorphosis in the Lepidoptera. Quart. J. Microscop. Sci 97, 215–233
    OpenUrl
    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. Golstein P.,
    2. Marguet D.,
    3. Depraetere V.
    (1995) Homology between Reaper and the cell death domains of Fas and TNFR1. Cell 81, 185–186
    OpenUrlCrossRefPubMedWeb of Science
    1. Grether M. E.,
    2. Abrams J. M.,
    3. Agapite J.,
    4. White K.,
    5. Steller H.
    (1995) The head involution defective gene of Drosophilamelanogaster functions in programmed cell death. Genes Dev 9, 1694–1708
    OpenUrlAbstract/FREE Full Text
    1. Gustafson K.,
    2. Boulianne G. L.
    (1996) Distinct expression patterns detected within individual tissues by the GAL4 enhancer trap technique. Genome 39, 174–182
    OpenUrlCrossRefPubMed
    1. Hay B. A.,
    2. Wassarman D. A.,
    3. Rubin G. M.
    (1995) Drosophila homologs of baculovirus inhibitor of apoptosis proteins function to block cell death. Cell 83, 1253–1262
    OpenUrlCrossRefPubMedWeb of Science
    1. Hay B. A.,
    2. Wolff T.,
    3. Rubin G. M.
    (1994) Expression of baculovirus P35 prevents cell death in Drosophila. Development 120, 2121–2129
    OpenUrlAbstract
    1. Helmberg A.,
    2. Auphan N.,
    3. Caelles C.,
    4. Karin M.
    (1995) Glucocorticoid-induced apoptosis of human leukemic cells is caused by the repressive function of the glucocorticoid receptor. EMBO J 14, 452–460
    OpenUrlPubMedWeb of Science
    1. Hurban P.,
    2. Thummel C. S.
    (1993) Isolation and characterization of fifteen ecdysone-inducible Drosophila genes reveal unexpected complexities in ecdysone regulation. Mol. Cell. Biol 13, 7101–7111
    OpenUrlAbstract/FREE Full Text
    1. Jacobson M. D.,
    2. Weil M.,
    3. Raff M. C.
    (1997) Programmed cell death in animal development. Cell 88, 347–354
    OpenUrlCrossRefPubMedWeb of Science
    1. Karim F. D.,
    2. Thummel C. S.
    (1992) Temporal coordination of regulatory gene expression by the steroid hormone ecdysone. EMBO J 11, 4083–4093
    OpenUrlPubMedWeb of Science
    1. Kerr J. F. R.,
    2. Wyllie A. H.,
    3. Currie A. R.
    (1972) Apoptosis: a basic biological phenomenon with wide ranging implications in tissue kinetics. Br. J. Cancer 26, 239–257
    OpenUrlCrossRefPubMedWeb of Science
    1. Liston P.,
    2. Roy N.,
    3. Tamai K.,
    4. Lefebvre C.,
    5. Baird S.,
    6. Cherton-Horvat G.,
    7. Farahani R.,
    8. McLean M.,
    9. Ikeda J. E.,
    10. MacKenzie A.,
    11. Korneluk R. G.
    (1996) Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes. Nature 379, 349–353
    OpenUrlCrossRefPubMedWeb of Science
    1. Lockshin R. A.,
    2. Williams C. M.
    (1964) Programmed cell death. II. Endocrine potentiation of the breakdown of the intersegmental muscles of silkmoths. J. Insect Physiol 10, 643–649
    OpenUrlCrossRef
    1. Lockshin R. A.,
    2. Williams C. M.
    (1965) Programmed cell death: I. Cytology of degeneration in the intersegmental muscles of the pernyi silkmoth. J. Insect Physiol 11, 123–133
    OpenUrlCrossRefPubMed
    1. Lockshin R. A.,
    2. Zakeri Z.
    (1994) Programmed cell death: early changes in metamorphosing cells. Biochem. Cell Biol 72, 589–596
    OpenUrlPubMed
    1. McAvoy J. W.,
    2. Dixon K. E.
    (1977) Cell proliferation and renewal in the small intestinal epithelium of metamorphosing and adult Xenopus laevis. J. Exp. Zool 202, 129–138
    OpenUrlCrossRef
    1. Nazareth L. V.,
    2. Harbour D. V.,
    3. Thompson E. B.
    (1991) Mapping the human glucocorticoid receptor for leukemic cell death. J. Biol. Chem 266, 12976–12980
    OpenUrlAbstract/FREE Full Text
    1. Pronk G. J.,
    2. Ramer K.,
    3. Amiri P.,
    4. Williams L. T.
    (1996) Requirement of an ICE-like protease for induction of apoptosis and ceramide generation by Reaper. Science 271, 808–810
    OpenUrlAbstract
    1. Rabizadeh S.,
    2. LaCount D. J.,
    3. Friesen P. D.,
    4. Bredesen D. E.
    (1993) Expression of the baculovirus p35 gene inhibits mammalian neural cell death. J. Neurochem 61, 2318–2321
    OpenUrlCrossRefPubMedWeb of Science
    1. Raff M. C.
    (1992) Social controls on cell survival and cell death. Nature 356, 397–400
    OpenUrlCrossRefPubMedWeb of Science
    1. Richards G.
    (1976) Sequential gene activation by ecdysone in polytene chromosomes of Drosophila melanogaster: V. The late prepupal puffs. Dev. Biol 54, 264–275
    OpenUrlCrossRefPubMedWeb of Science
    1. Robertson C. W.
    (1936) The metamorphosis of Drosophila melanogaster, including an accurately timed account of the principal morphological changes. J. Morph 59, 351–399
    OpenUrlCrossRefWeb of Science
    1. Robinow S.,
    2. Talbot W. S.,
    3. Hogness D. S.,
    4. Truman J. W.
    (1993) Programmed cell death in the Drosophila CNS is ecdysone-regulated and coupled with a specific ecdysone receptor isoform. Development 119, 1251–1259
    OpenUrlAbstract
    1. Rothe M.,
    2. Pan M. G.,
    3. Henzel W. J.,
    4. Ayres T. M.,
    5. Goeddel D. V.
    (1995) The TNFR2-TRAF signaling complex contains two novel proteins related to baculovirus inhibitor of apoptosis proteins. Cell 83, 1243–1252
    OpenUrlCrossRefPubMedWeb of Science
    1. Schwartz L. M.,
    2. Truman J. W.
    (1982) Peptide and steroid regulation of muscle degeneration in an insect. Science 215, 1420–1421
    OpenUrlAbstract/FREE Full Text
    1. Shi Y. B.,
    2. Brown D. D.
    (1993) The earliest changes in gene expression in tadpole intestine induced by thyroid hormone. J. Biol. Chem 268, 20312–20317
    OpenUrlAbstract/FREE Full Text
    1. Smith A. V.,
    2. Orr-Weaver T. L.
    (1991) The regulation of the cell cycle during Drosophila embryogenesis: the transition to polyteny. Development 112, 997–1008
    OpenUrlAbstract
    1. Steller H.
    (1995) Mechanisms and genes of cellular suicide. Science 267, 1445–1449
    OpenUrlAbstract/FREE Full Text
    1. Sugimoto A.,
    2. Friesen P. D.,
    3. Rothman J. H.
    (1994) Baculovirus p35 prevents developmentally regulated cell death and rescues a ced-9 mutant in the nematode Caenorhabditis elegans. EMBO J 13, 2023–2028
    OpenUrlPubMedWeb of Science
    1. Talbot W. S.,
    2. Swyryd E. A.,
    3. Hogness D. S.
    (1993) Drosophila tissues with different metamorphic responses to ecdysone express different ecdysone receptor isoforms. Cell 73, 1323–1337
    OpenUrlCrossRefPubMedWeb of Science
    1. Thummel C. S.
    (1996) Flies on steroids—Drosophila metamorphosis and the mechanisms of steroid hormone action. Trends Genet 12, 306–310
    OpenUrlCrossRefPubMedWeb of Science
    1. Truman J. W.,
    2. Talbot W. S.,
    3. Fahrbach S. E.,
    4. Hogness D. S.
    (1994) Ecdysone receptor expression in the CNS correlates with stage-specific responses to ecdysteroids during Drosophila and Manduca development. Development 120, 219–234
    OpenUrlAbstract
    1. Truman J. W.,
    2. Thorn R. S.,
    3. Robinow S.
    (1992) Programmed neuronal death in insect development. J. Neurol 23, 1295–1311
    OpenUrl
    1. Ucker D. S.
    (1987) Cytotoxic T lymphocytes and glucocorticoids activate an endogenous suicide process in target cells. Nature 327, 62–64
    OpenUrlCrossRefPubMed
    1. Uren A. G.,
    2. Pakusch M.,
    3. Hawkins C. J.,
    4. Puls K. L.,
    5. Vaux D. L.
    (1996) Cloning and expression of apoptosis inhibitory protein homologs that function to inhibit apoptosis and/or bind tumor necrosis factor receptor-associated factors. Proc. Natl. Acad. Sci. USA 93, 4974–4978
    OpenUrlAbstract/FREE Full Text
    1. Urness L. D.,
    2. Thummel C. S.
    (1995) Molecular analysis of a steroid-induced regulatory hierarchy: the Drosophila E74A protein directly regulates L71-6 transcription. EMBO J 14, 6239–6246
    OpenUrlPubMedWeb of Science
    1. Weeks J. C.,
    2. Truman J. W.
    (1985) Independent steroid control of the fates of motoneurons and their muscles during insect metamorphosis. J. Neurosci 5, 2290–2300
    OpenUrlAbstract
    1. White K.,
    2. Grether M. E.,
    3. Abrams J. M.,
    4. Young L.,
    5. Farrell K.,
    6. Steller H.
    (1994) Genetic control of programmed cell death in Drosophila. Science 264, 677–683
    OpenUrlAbstract/FREE Full Text
    1. White K.,
    2. Tahaoglu E.,
    3. Steller H.
    (1996) Cell killing by the Drosophila gene reaper. Science 271, 805–807
    OpenUrlAbstract
    1. White K. P.,
    2. Hurban P.,
    3. Watanabe T.,
    4. Hogness D. S.
    (1997) Coordination of Drosophila metamorphosis by two ecdysone-induced nuclear receptors. Science 276, 114–117
    OpenUrlAbstract/FREE Full Text
    1. Wolff T.,
    2. Ready D. F.
    (1991) Cell death in normal and rough eye mutants of Drosophila. Development 113, 825–839
    OpenUrlAbstract
    1. Woodard C. T.,
    2. Baehrecke E. H.,
    3. Thummel C. S.
    (1994) A molecular mechanism for the stage-specificity of the Drosophila prepupal genetic response to ecdysone. Cell 79, 607–615
    OpenUrlCrossRefPubMedWeb of Science
    1. Wyllie A. H.
    (1980) Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 284, 555–556
    OpenUrlCrossRefPubMedWeb of Science
    1. Xue D.,
    2. Horvitz H. R.
    (1995) Inhibition of the Caenorhabditis elegans cell-death protease CED-3 by a CED-3 cleavage site in baculovirus p35 protein. Nature 377, 248–251
    OpenUrlCrossRefPubMedWeb of Science
Back to top

 Download PDF

Email
JOURNAL ARTICLES
Steroid regulated programmed cell death during Drosophila metamorphosis
C. Jiang, E.H. Baehrecke, C.S. Thummel
Development 1997 124: 4673-4683;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Alerts

Article navigation

Other journals from The Company of Biologists

Advertisement

An interview with Swathi Arur

Swathi Arur joined the team at Development as an Academic Editor in 2020. Her lab uses multidisciplinary approaches to understand female germline development and fertility. We met with her over Zoom to hear more about her life, her career and her love for C. elegans.

Jim Wells and Hanna Mikkola join our team of Editors

We are pleased to welcome James (Jim) Wells and Hanna Mikkola to our team of Editors. Jim joins us a new Academic Editor, taking over from Gordan Keller, and Hanna joins our team of Associate Editors. Find out more about their research interests and areas of expertise.

New funding scheme supports sustainable events

As part of our Sustainable Conferencing Initiative, we are pleased to announce funding for organisers that seek to reduce the environmental footprint of their event. The next deadline to apply for a Scientific Meeting grant is 26 March 2021.

Read & Publish participation continues to grow

“I’d heard of Read & Publish deals and knew that many universities, including mine, had signed up to them but I had not previously understood the benefits that these deals bring to authors who work at those universities.”

Professor Sally Lowell (University of Edinburgh) shares her experience of publishing Open Access as part of our growing Read & Publish initiative. We now have over 150 institutions in 15 countries and four library consortia taking part – find out more and view our full list of participating institutions.

Upcoming special issues

Imaging Development, Stem Cells and Regeneration
Submission deadline: 30 March 2021
Publication: mid-2021

The Immune System in Development and Regeneration
Guest editors: Florent Ginhoux and Paul Martin
Submission deadline: 1 September 2021
Publication: Spring 2022

Both special issues welcome Review articles as well as Research articles, and will be widely promoted online and at key global conferences.

Development presents...

Our successful webinar series continues into 2021, with early-career researchers presenting their papers and a chance to virtually network with the developmental biology community afterwards. Here, Brandon Carpenter talks about how inherited histone methylation defines the germline versus soma decision in C. elegans. 

Sign up to join our next session:

10 March
Time: TBC
Chaired by: Thomas Lecuit