Advertisement
JOURNAL ARTICLES
Steroid regulation of autophagic programmed cell death during development
C.Y. Lee, E.H. Baehrecke
Development 2001 128: 1443-1455;

Summary

Apoptosis and autophagy are morphologically distinct forms of programmed cell death. While autophagy occurs during the development of diverse organisms and has been implicated in tumorigenesis, little is known about the molecular mechanisms that regulate this type of cell death. Here we show that steroid-activated programmed cell death of Drosophila salivary glands occurs by autophagy. Expression of p35 prevents DNA fragmentation and partially inhibits changes in the cytosol and plasma membranes of dying salivary glands, suggesting that caspases are involved in autophagy. The steroid-regulated BR-C, E74A and E93 genes are required for salivary gland cell death. BR-C and E74A mutant salivary glands exhibit vacuole and plasma membrane breakdown, but E93 mutant salivary glands fail to exhibit these changes, indicating that E93 regulates early autophagic events. Expression of E93 in embryos is sufficient to induce cell death with many characteristics of apoptosis, but requires the H99 genetic interval that contains the rpr, hid and grim proapoptotic genes to induce nuclear changes diagnostic of apoptosis. In contrast, E93 expression is sufficient to induce the removal of cells by phagocytes in the absence of the H99 genes. These studies indicate that apoptosis and autophagy utilize some common regulatory mechanisms.

Reference

    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. Andres A. J.,
    2. Thummel C. S.
    (1992) Hormones, puffs, and flies: the molecular control of metamorphosis by ecdysone. Trends Genet 8, 132–138
    OpenUrlCrossRefPubMed
    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.
    (1997) who encodes a KH RNA binding protein that functions in muscle development. Development 124, 1323–1332
    OpenUrlAbstract
    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. Baker Brachmann C.,
    2. Jassim O. W.,
    3. Wachsmuth B. D.,
    4. Cagan R.L.
    (2000) The Drosophila Bcl-2 family member dBorg-1 functions in the apototic response to UV-irradiation. Current Biol 10, 547–550
    OpenUrlCrossRefPubMedWeb of Science
    1. Becker H. J.
    (1959) Die puffs der speicheldrusenchromosomen von Drosophila melanogaster. I. Beobachtungen zur verhalten des puffmusters in normalstamm und bei zwei mutanten, giant und lethal-giant-larvae. Chromosoma 10, 654–678
    1. Bender M.,
    2. Imam F. B.,
    3. Talbot W. S.,
    4. Ganetzky B.,
    5. Hogness D. S.
    (1997) Drosophila ecdysone receptor mutations reveal functional differences among receptor isoforms. Cell 91, 777–788
    OpenUrlCrossRefPubMedWeb of Science
    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. Broadus J.,
    2. McCabe J. R.,
    3. Endrizzi B.,
    4. Thummel C. S.,
    5. Woodard C. T.
    (1999) The Drosophila FTZ-F1 orphan nuclear receptor provides competence for stage-specific responses to the steroid hormone ecdysone. Mol. Cell 3, 143–149
    OpenUrlCrossRef
    1. Bursch W.,
    2. Ellinger A.,
    3. Kienzl H.,
    4. Torok L.,
    5. Pandey S.,
    6. Sikorska M.,
    7. Walker R.,
    8. Hermann R. S.
    (1996) Active cell death induced by the anti-estrogens tamoxifen and ICI164384 in human mammary carcinoma cells (MCF-7) in culture: the role of autophagy. Carcinogenesis 17, 1595–1607
    OpenUrlAbstract/FREE Full Text
    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. Chen P.,
    2. Rodriguez A.,
    3. Erskine R.,
    4. Thach T.,
    5. Abrams J. M.
    (1998) Dredd, a novel effector of the apoptosis activators Reaper, Grim, and Hid in Drosophila. Dev. Biol 201, 202–216
    OpenUrlCrossRefPubMedWeb of Science
    1. Clarke P. G. H.
    (1990) Developmental cell death: morphological diversity and multiple mechanisms. Anat. Embryol 181, 195–213
    OpenUrlPubMed
    1. Clever U.
    (1964) Actinomycin and puromycin: effects on sequential gene activation by ecdysone. Science 146, 794–795
    OpenUrlAbstract/FREE Full Text
    1. Colussi P. A.,
    2. Quinn L. M.,
    3. Huang D. C. S.,
    4. Coombe M.,
    5. Read S. H.,
    6. Richardson H.,
    7. Kumar S.
    (2000) Debcl, a proapoptotic Bcl-2 homologue, is a component of the Drosophila melanogaster cell death machinery. J. Cell Biol 148, 703–714
    OpenUrlAbstract/FREE Full Text
    1. Dorstyn L.,
    2. Colussi P. A.,
    3. Quinn L. M.,
    4. Richardson H.,
    5. Kumar S.
    (1999) DRONC, an ecdysone-inducible Drosophila caspase. Proc. Natl. Acad. Sci. USA 96, 4307–4312
    OpenUrlAbstract/FREE Full Text
    1. Dorstyn L.,
    2. Read S. H.,
    3. Quinn L. M.,
    4. Richardson H.,
    5. Kumar S.
    (1999) DECAY, a novel Drosophila caspase related to mammalian caspase-3 and caspase-7. J. Biol. Chem 274, 30778–30783
    OpenUrlAbstract/FREE Full Text
    1. Evans-Storm R. B.,
    2. Cidlowski J. A.
    (1995) Regulation of apoptosis by steroid hormones. J. Steroid Biochem. Molec. Biol 53, 1–6
    1. Fletcher J. C.,
    2. Burtis K. C.,
    3. Hogness D. S.,
    4. Thummel C. S.
    (1995) The DrosophilaE74 gene is required for metamorphosis and plays a role in the polytene chromosome puffing response to ecdysone. Development 121, 1455–1465
    OpenUrlAbstract
    1. Foley K.,
    2. Cooley L.
    (1998) Apoptosis in late stage Drosophila nurse cells does not require genes within the H99 deficiency. Development 125, 1075–1082
    OpenUrlAbstract
    1. Franc N. C.,
    2. Dimarcq J.-L.,
    3. Lagueux M.,
    4. Hoffmann J.,
    5. Ezekowitz A. B.
    (1996) Croquemort, a novel Drosophila hemocyte/macrophage receptor that recognizes apoptotic cells. Immunity 4, 431–443
    OpenUrlCrossRefPubMedWeb of Science
    1. Franc N. C.,
    2. Heitzler P.,
    3. Ezekowitz A. B.,
    4. White K.
    (1999) Requirement for Croquemort in phagocytosis of apoptotic cells in Drosophila. Science 284, 1991–1994
    OpenUrlAbstract/FREE Full Text
    1. Fraser A. G.,
    2. Evan G. I.
    (1997) Identification of a Drosophila melanogaster ICE/CED-3-related protease, drICE. EMBO J 16, 2805–2813
    OpenUrlAbstract
    1. Goyal L.,
    2. McCall K.,
    3. Agapite J.,
    4. Hartwieg E.,
    5. Steller H.
    (2000) Induction of apoptosis by Drosophila reaper, hid and grim through inhibition of IAP function. EMBO J 19, 589–597
    OpenUrlAbstract
    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. Haining W. N.,
    2. Carboy-Newcomb C.,
    3. Wei C. L.,
    4. Steller H.
    (1999) The proapoptotic function of Drosophila Hid is conserved in mammalian cells. Proc. Natl. Acad. Sci. USA 96, 4936–4941
    OpenUrlAbstract/FREE Full Text
    1. Hall B. L.,
    2. Thummel C. S.
    (1998) The RXR homolog Ultraspiracle is an essential component of the Drosophila ecdysone receptor. Development 125, 4709–4717
    OpenUrlAbstract
    1. Hawkins C. J.,
    2. Yoo S. J.,
    3. Peterson E. P.,
    4. Wang S. L.,
    5. Vernooy S. Y.,
    6. Hay B. A.
    (2000) The Drosophila caspase DRONC cleaves following glutamate or aspartate and is regulated by DIAP1, HID and GRIM. J. Biol. Chem 275, 27084–27093
    OpenUrlAbstract/FREE Full Text
    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. Igaki T.,
    2. Kanuka H.,
    3. Inohara N.,
    4. Sawamoto K.,
    5. Nunez G.,
    6. Okano H.,
    7. Miura M.
    (2000) Drob-1, a Drosophila member of the Bcl-2/CED-9 family that promotes cell death. Proc. Natl. Acad. Sci. USA 97, 662–667
    OpenUrlAbstract/FREE Full Text
    1. Inohara N.,
    2. Koseki T.,
    3. Hu Y.,
    4. Chen S.,
    5. Nunez G.
    (1997) CLARP, a death effector domain-containing protein interacts with caspase-8 and regulates apoptosis. Proc. Natl. Acad. Sci. USA 94, 10717–10722
    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. Jiang C.,
    2. Baehrecke E. H.,
    3. Thummel C. S.
    (1997) Steroid regulated programmed cell death during Drosophila metamorphosis. Development 124, 4673–4683
    OpenUrlAbstract
    1. Jiang C.,
    2. Lamblin A.-F. J.,
    3. Steller H.,
    4. Thummel C. S.
    (2000) Asteroid-triggered transcriptional hierarchy controls salivary gland cell death during Drosophila metamorphosis. Mol. Cell 5, 445–455
    OpenUrlCrossRef
    1. Kanuka H.,
    2. Sawamoto K.,
    3. Inohara N.,
    4. Matsuno K.,
    5. Okano H.,
    6. Miura M.
    (1999) Control of the cell death pathway by Dapaf-1, a Drosophila Apaf-1/CED-4-related caspase activator. Mol. Cell 4, 757–769
    OpenUrl
    1. Kerr J. F.,
    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. Kondo T.,
    2. Yokokura T.,
    3. Nagata S.
    (1997) Activation of distinct caspase-like proteases by Fas and reaper in Drosophila cells. Proc. Natl. Acad. Sci. USA 94, 11951–11956
    OpenUrlAbstract/FREE Full Text
    1. Lee C.-Y.,
    2. Wendel D. P.,
    3. Reid P.,
    4. Lam G.,
    5. Thummel C. S.,
    6. Baehrecke E. H.
    (2000) E93 directs steroid-triggered programmed cell death in Drosophila. Mol. Cell 6, 433–443
    OpenUrl
    1. Liang X. H.,
    2. Jackson S.,
    3. Seaman M.,
    4. Brown K.,
    5. Kempkes B.,
    6. Hibshoosh H.,
    7. Levine B.
    (1999) Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402, 672–676
    OpenUrlCrossRefPubMedWeb of Science
    1. Lisi S.,
    2. Mazzon I.,
    3. White K.
    (2000) Diverse domains of THREAD/DIAP1 are required to inhibit apoptosis induced by REAPER and HID in Drosophila. Genetics 154, 669–678
    OpenUrlAbstract/FREE Full Text
    1. McCall K.,
    2. Steller H.
    (1998) Requirement for DCP-1 caspase during Drosophila oogenesis. Science 279, 230–234
    OpenUrlAbstract/FREE Full Text
    1. McCarthy J. C.,
    2. Dixit V. M.
    (1998) Apoptosis induced by Drosophila Reaper and Grim in a human system. J. Biol. Chem 273, 24009–24015
    OpenUrlAbstract/FREE Full Text
    1. McCarthy N. J.,
    2. Whyte M. K. B.,
    3. Gilbert C. S.,
    4. Evan G. I.
    (1997) Inhibition of Ced-3/ICE-related proteases does not prevent cell death induced by oncogenes, DNA damage, or the Bcl-2 homologue Bak. J. Cell Biol 136, 215–227
    OpenUrlAbstract/FREE Full Text
    1. Meier P.,
    2. Silke J.,
    3. Leevers S. J.,
    4. Evan G. I.
    (2000) The Drosophila caspase DRONC is regulated by DIAP1. EMBO J 19, 598–611
    OpenUrlAbstract/FREE Full Text
    1. Mills J. C.,
    2. Stone N. L.,
    3. Erhardt J.,
    4. Pittman R. N.
    (1998) Apoptotic membrane blebbing is regulated by myosin light chain phosphorylation. J. Cell Biol 140, 627–636
    OpenUrlAbstract/FREE Full Text
    1. Nusslein-Volhard C.,
    2. Wieschaus E.
    (1980) Mutations affecting segment number and polarity in Drosophila. Nature 287, 795–801
    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. Saunders J. W.
    (1966) Death in embryonic systems. Science 154, 604–612
    OpenUrlAbstract/FREE Full Text
    1. Schulte-Hermann R.,
    2. Bursch W.,
    3. Grasl-Kraupp B.,
    4. Marian B.,
    5. Torok L.,
    6. Kahl-Rainer P.,
    7. Ellinger A.
    (1997) Concepts of cell death and application to carcinogenesis. Toxicol. Pathol 25, 89–93
    OpenUrlAbstract/FREE Full Text
    1. Schwartz L. M.,
    2. Smith S. W.,
    3. Jones M. E. E.,
    4. Osborne B. A.
    (1993) Do all programmed cell deaths occur via apoptosis?. Proc. Natl. Acad. Sci. USA 90, 980–984
    OpenUrlAbstract/FREE Full Text
    1. Schweichel J.-U.,
    2. Merker H.-J.
    (1973) The morphology of various types of cell death in prenatal tissues. Teratology 7, 253–266
    OpenUrlCrossRefPubMed
    1. Song Z.,
    2. McCall K.,
    3. Steller H.
    (1997) DCP-1, a Drosophila cell death protease essential for development. Science 275, 536–540
    OpenUrlAbstract/FREE Full Text
    1. Thompson C. B.
    (1995) Apoptosis in the pathogenesis and treatment of disease. Science 267, 1456–1462
    OpenUrlAbstract/FREE Full Text
    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. Vaux D. L.,
    2. Korsmeyer S. J.
    (1999) Cell death in development. Cell 96, 245–254
    OpenUrlCrossRefPubMedWeb of Science
    1. von Gaudecker B.,
    2. Schmale E.-M.
    (1974) Substrate-histochemical investigations and ultrahistochemical demonstrations of acid phosphatase in larval and prepupal salivary glands of Drosophila melanogasater. Cell Tiss. Res 155, 75–89
    OpenUrlPubMedWeb of Science
    1. Wang S. L.,
    2. Hawkins C. J.,
    3. Yoo S. J.,
    4. Muller H.-A. J.,
    5. Hay B. A.
    (1999) The Drosophila caspase inhibitor DIAP1 is essential for cell survival and is negatively regulated by HID. Cell 98, 453–463
    OpenUrlCrossRefPubMedWeb of Science
    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. Woo M.,
    2. Hakem R.,
    3. Soengas M. S.,
    4. Duncan G. S.,
    5. Shahinian A.,
    6. Kagi D.,
    7. Hakem A.,
    8. McCurrach M.,
    9. Khoo W.,
    10. Kaufman S. A.,
    11. et al
    . (1998) Essential contribution of caspase 3/CPP32 to apoptosis and its nuclear changes. Genes Dev 12, 806–819
    OpenUrlAbstract/FREE Full Text
    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. Yang Y.,
    2. Fang S.,
    3. Jensen J. P.,
    4. Weissman A. M.,
    5. Ashwell J. D.
    (2000) Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli. Science 288, 874–877
    OpenUrlAbstract/FREE Full Text
    1. Zhou L.,
    2. Song Z.,
    3. Tittel J.,
    4. Steller H.
    (1999) HAC-1, a Drosophila homolog of APAF-1 and CED-4, functions in developmental and radiation-induced apoptosis. Mol. Cell 4, 745–755
    OpenUrl
Back to top

 Download PDF

Email
JOURNAL ARTICLES
Steroid regulation of autophagic programmed cell death during development
C.Y. Lee, E.H. Baehrecke
Development 2001 128: 1443-1455;
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