Genetic Control of Programmed Cell Death in Drosophila
10.1126/science.8171319
Crossref journal-article
American Association for the Advancement of Science (AAAS)
Science (221)
Abstract

A gene, reaper ( rpr ), that appears to play a central control function for the initiation of programmed cell death (apoptosis) in Drosophila was identified. Virtually all programmed cell death that normally occurs during Drosophila embryogenesis was blocked in embryos homozygous for a small deletion that includes the reaper gene. Mutant embryos contained many extra cells and failed to hatch, but many other aspects of development appeared quite normal. Deletions that include reaper also protected embryos from apoptosis caused by x-irradiation and developmental defects. However, high doses of x-rays induced some apoptosis in mutant embryos, and the resulting corpses were phagocytosed by macrophages. These data suggest that the basic cell death program is intact although it was not activated in mutant embryos. The DNA encompassed by the deletion was cloned and the reaper gene was identified on the basis of the ability of cloned DNA to restore apoptosis to cell death defective embryos in germ line transformation experiments. The reaper gene appears to encode a small peptide that shows no homology to known proteins, and reaper messenger RNA is expressed in cells destined to undergo apoptosis.

Bibliography

White, K., Grether, M. E., Abrams, J. M., Young, L., Farrell, K., & Steller, H. (1994). Genetic Control of Programmed Cell Death in Drosophila. Science, 264(5159), 677–683.

Authors 6
  1. Kristin White (first)
  2. Megan E. Grether (additional)
  3. John M. Abrams (additional)
  4. Lynn Young (additional)
  5. Kim Farrell (additional)
  6. Hermann Steller (additional)
References 62 Referenced 891
  1. ABBOTT, M.K., EMBRYONIC HEAD INVOLUTION AND ROTATION OF MALE TERMINALIA REQUIRE THE DROSOPHILA LOCUS HEAD INVOLUTION DEFECTIVE, GENETICS 129: 783 (1991). (10.1093/genetics/129.3.783) / GENETICS (1991)
  2. 10.1242/dev.117.1.29
  3. ABRAMS J.M. unpublished data.
  4. ALLSOPP, T.E., THE PROTOONCOGENE BCL-2 CAN SELECTIVELY RESCUE NEUROTROPHIC FACTOR-DEPENDENT NEURONS FROM APOPTOSIS, CELL 73: 295 (1993). (10.1016/0092-8674(93)90230-N) / CELL (1993)
  5. Ashburner M. Drosophila: A Laboratory Manual (1989).
  6. BALDARELLI, R.M., TRANSCRIPTS OF THE DROSOPHILA BLASTODERM-SPECIFIC LOCUS, TERMINUS, ARE CONCENTRATED POSTERIORLY AND ENCODE A POTENTIAL DNA-BINDING FINGER, DEVELOPMENTAL BIOLOGY 125: 85 (1988). (10.1016/0012-1606(88)90061-9) / DEVELOPMENTAL BIOLOGY (1988)
  7. BARRES, B.A., CELL-DEATH AND CONTROL OF CELL-SURVIVAL IN THE OLIGODENDROCYTE LINEAGE, CELL 70: 31 (1992). (10.1016/0092-8674(92)90531-G) / CELL (1992)
  8. BATE, C.M., EMBRYOGENESIS OF AN INSECT NERVOUS-SYSTEM .1. MAP OF THORACIC AND ABDOMINAL NEUROBLASTS IN LOCUSTA-MIGRATORIA, JOURNAL OF EMBRYOLOGY AND EXPERIMENTAL MORPHOLOGY 35: 107 (1976). / JOURNAL OF EMBRYOLOGY AND EXPERIMENTAL MORPHOLOGY (1976)
  9. BATE, M, EMBRYONIC-DEVELOPMENT OF IDENTIFIED NEURONS - SEGMENT-SPECIFIC DIFFERENCES IN THE H-CELL HOMOLOGS, JOURNAL OF NEUROSCIENCE 1: 103 (1981). (10.1523/JNEUROSCI.01-01-00103.1981) / JOURNAL OF NEUROSCIENCE (1981)
  10. BONINI, N.M., THE EYES ABSENT GENE - GENETIC-CONTROL OF CELL-SURVIVAL AND DIFFERENTIATION IN THE DEVELOPING DROSOPHILA EYE, CELL 72: 379 (1993). (10.1016/0092-8674(93)90115-7) / CELL (1993)
  11. BRAY, S.J., EMBRYONIC EXPRESSION PATTERN OF A FAMILY OF DROSOPHILA PROTEINS THAT INTERACT WITH A CENTRAL NERVOUS-SYSTEM REGULATORY ELEMENT, GENES & DEVELOPMENT 3: 1130 (1989). (10.1101/gad.3.8.1130) / GENES & DEVELOPMENT (1989)
  12. CAGAN, R.L., NOTCH IS REQUIRED FOR SUCCESSIVE CELL DECISIONS IN THE DEVELOPING DROSOPHILA RETINA, GENES & DEVELOPMENT 3: 1099 (1989). (10.1101/gad.3.8.1099) / GENES & DEVELOPMENT (1989)
  13. CAMPOS A.R. unpublished data.
  14. Campos-Ortega J. A. The Embryonic Development of Drosophila melanogaster (1985). (10.1007/978-3-662-02454-6)
  15. CAVANER, R, NUCLEIC ACIDS RES 15: 1353 (1987). (10.1093/nar/15.4.1353) / NUCLEIC ACIDS RES (1987)
  16. 10.1038/362849a0
  17. CMAPOS, K.F., DEVELOPMENT 114: 355 (1992). (10.1242/dev.114.2.355) / DEVELOPMENT (1992)
  18. 10.1126/science.6474175
  19. ELLIS, R.E., MECHANISMS AND FUNCTIONS OF CELL-DEATH, ANNUAL REVIEW OF CELL BIOLOGY 7: 663 (1991). (10.1146/annurev.cb.07.110191.003311) / ANNUAL REVIEW OF CELL BIOLOGY (1991)
  20. FISCHBACH, K.F., CELL DEGENERATION IN THE DEVELOPING OPTIC LOBES OF THE SINE OCULIS AND SMALL-OPTIC-LOBES MUTANTS OF DROSOPHILA-MELANOGASTER, DEVELOPMENTAL BIOLOGY 104: 219 (1984). (10.1016/0012-1606(84)90050-2) / DEVELOPMENTAL BIOLOGY (1984)
  21. FREEMAN, R.S., CURR OPIN NEUROBIOL 3: 25 (1993). (10.1016/0959-4388(93)90031-S) / CURR OPIN NEUROBIOL (1993)
  22. FRISTROM, D, MOLECULAR AND GENERAL GENETICS 103: 363 (1969). (10.1007/BF00383486) / MOLECULAR AND GENERAL GENETICS (1969)
  23. GARCIABELLIDO, A, THE EFFECT OF ANEUPLOIDY ON EMBRYONIC-DEVELOPMENT IN DROSOPHILA-MELANOGASTER, MOLECULAR & GENERAL GENETICS 192: 253 (1983). (10.1007/BF00327675) / MOLECULAR & GENERAL GENETICS (1983)
  24. GAUL, U, ANALYSIS OF KRUPPEL PROTEIN DISTRIBUTION DURING EARLY DROSOPHILA DEVELOPMENT REVEALS POSTTRANSCRIPTIONAL REGULATION, CELL 50: 639 (1987). (10.1016/0092-8674(87)90037-7) / CELL (1987)
  25. GAVRIELI, Y, IDENTIFICATION OF PROGRAMMED CELL-DEATH INSITU VIA SPECIFIC LABELING OF NUCLEAR-DNA FRAGMENTATION, JOURNAL OF CELL BIOLOGY 119: 493 (1992). (10.1083/jcb.119.3.493) / JOURNAL OF CELL BIOLOGY (1992)
  26. GIORGI, F, CELL-DEATH IN OVARIAN CHAMBERS OF DROSOPHILA-MELANOGASTER, JOURNAL OF EMBRYOLOGY AND EXPERIMENTAL MORPHOLOGY 35: 521 (1976). / JOURNAL OF EMBRYOLOGY AND EXPERIMENTAL MORPHOLOGY (1976)
  27. GRETHER M unpublished data.
  28. HAMBURGER, V, CELL-DEATH IN DEVELOPMENT OF LATERAL MOTOR COLUMN OF CHICK-EMBRYO, JOURNAL OF COMPARATIVE NEUROLOGY 160: 535 (1975). (10.1002/cne.901600408) / JOURNAL OF COMPARATIVE NEUROLOGY (1975)
  29. HOCKENBERY, D, BCL-2 IS AN INNER MITOCHONDRIAL-MEMBRANE PROTEIN THAT BLOCKS PROGRAMMED CELL-DEATH, NATURE 348: 334 (1990). (10.1038/348334a0) / NATURE (1990)
  30. KERR, JFR, APOPTOSIS - BASIC BIOLOGICAL PHENOMENON WITH WIDE-RANGING IMPLICATIONS IN TISSUE KINETICS, BRITISH JOURNAL OF CANCER 26: 239 (1972). (10.1038/bjc.1972.33) / BRITISH JOURNAL OF CANCER (1972)
  31. KIMURA, K, POSTMETAMORPHIC CELL-DEATH IN THE NERVOUS AND MUSCULAR SYSTEMS OF DROSOPHILA-MELANOGASTER, JOURNAL OF NEUROSCIENCE 10: 403 (1990). (10.1523/JNEUROSCI.10-02-00403.1990) / JOURNAL OF NEUROSCIENCE (1990)
  32. KLINGENSMITH, J, THE SEGMENT POLARITY PHENOTYPE OF DROSOPHILA INVOLVES DIFFERENTIAL TENDENCIES TOWARD TRANSFORMATION AND CELL-DEATH, DEVELOPMENTAL BIOLOGY 134: 130 (1989). (10.1016/0012-1606(89)90084-5) / DEVELOPMENTAL BIOLOGY (1989)
  33. 10.1093/nar/12.2.857
  34. LOCKSHIN, R.A., PROGRAMMED CELL DEATH . ACTIVATION OF LYSIS BY A MECHANISM INVOLVING SYNTHESIS OF PROTEIN, JOURNAL OF INSECT PHYSIOLOGY 15: 1505 (1969). (10.1016/0022-1910(69)90172-3) / JOURNAL OF INSECT PHYSIOLOGY (1969)
  35. 10.1038/362847a0
  36. MACKAY, W.J., THE GENETICS OF CATALASE IN DROSOPHILA-MELANOGASTER - ISOLATION AND CHARACTERIZATION OF ACATALASEMIC MUTANTS, GENETICS 122: 643 (1989). (10.1093/genetics/122.3.643) / GENETICS (1989)
  37. MAGRASSI, L, THE PATTERN OF CELL-DEATH IN FUSHI-TARAZU, A SEGMENTATION GENE OF DROSOPHILA, DEVELOPMENT 104: 447 (1988). (10.1242/dev.104.3.447) / DEVELOPMENT (1988)
  38. MARTIN, D.P., INHIBITORS OF PROTEIN-SYNTHESIS AND RNA-SYNTHESIS PREVENT NEURONAL DEATH CAUSED BY NERVE GROWTH-FACTOR DEPRIVATION, JOURNAL OF CELL BIOLOGY 106: 829 (1988). (10.1083/jcb.106.3.829) / JOURNAL OF CELL BIOLOGY (1988)
  39. MARTINEZARIAS, A, THE DEVELOPMENT OF FUSED-EMBRYOS OF DROSOPHILA-MELANOGASTER, JOURNAL OF EMBRYOLOGY AND EXPERIMENTAL MORPHOLOGY 87: 99 (1985). / JOURNAL OF EMBRYOLOGY AND EXPERIMENTAL MORPHOLOGY (1985)
  40. MURPHY, C, CELL-DEATH AND AUTONOMOUS GENE ACTION IN LETHALS AFFECTING IMAGINAL DISKS IN DROSOPHILA-MELANOGASTER, DEVELOPMENTAL BIOLOGY 39: 23 (1974). (10.1016/S0012-1606(74)80005-9) / DEVELOPMENTAL BIOLOGY (1974)
  41. OPPENHEIM, R.W., CELL-DEATH DURING DEVELOPMENT OF THE NERVOUS-SYSTEM, ANNUAL REVIEW OF NEUROSCIENCE 14: 453 (1991). (10.1146/annurev.ne.14.030191.002321) / ANNUAL REVIEW OF NEUROSCIENCE (1991)
  42. OPPENHEIM, R.W., NATURALLY-OCCURRING AND INDUCED NEURONAL DEATH IN THE CHICK-EMBRYO INVIVO REQUIRES PROTEIN AND RNA-SYNTHESIS - EVIDENCE FOR THE ROLE OF CELL-DEATH GENES, DEVELOPMENTAL BIOLOGY 138: 104 (1990). (10.1016/0012-1606(90)90180-Q) / DEVELOPMENTAL BIOLOGY (1990)
  43. POTTEN, C.S., DIFFERENTIAL RADIATION RESPONSE AMONGST PROLIFERATING EPITHELIAL-CELLS, CELL AND TISSUE KINETICS 11: 149 (1978). / CELL AND TISSUE KINETICS (1978)
  44. PROKOP, A, THE ORIGIN OF POSTEMBRYONIC NEUROBLASTS IN THE VENTRAL NERVE CORD OF DROSOPHILA-MELANOGASTER, DEVELOPMENT 111: 79 (1991). (10.1242/dev.111.1.79) / DEVELOPMENT (1991)
  45. 10.1038/356397a0
  46. 10.1126/science.8235590
  47. ROBERTSON, H.M., A STABLE GENOMIC SOURCE OF P-ELEMENT TRANSPOSASE IN DROSOPHILA-MELANOGASTER, GENETICS 118: 461 (1988). (10.1093/genetics/118.3.461) / GENETICS (1988)
  48. SCHWARTZ, L.M., GENE ACTIVATION IS REQUIRED FOR DEVELOPMENTALLY PROGRAMMED CELL-DEATH, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 87: 6594 (1990). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1990)
  49. SEGRAVES, W.A., THE E75 ECDYSONE-INDUCIBLE GENE RESPONSIBLE FOR THE 75B EARLY PUFF IN DROSOPHILA ENCODES 2 NEW MEMBERS OF THE STEROID-RECEPTOR SUPERFAMILY, GENES & DEVELOPMENT 4: 204 (1990). (10.1101/gad.4.2.204) / GENES & DEVELOPMENT (1990)
  50. STELLER, H, DISCONNECTED - A LOCUS REQUIRED FOR NEURONAL PATHWAY FORMATION IN THE VISUAL-SYSTEM OF DROSOPHILA, CELL 50: 1139 (1987). (10.1016/0092-8674(87)90180-2) / CELL (1987)
  51. TATA, J.R., REQUIREMENT FOR RNA AND PROTEIN SYNTHESIS FOR INDUCED REGRESSION OF TADPOLE TAIL IN ORGAN CULTURE, DEVELOPMENTAL BIOLOGY 13: 77 (1966). (10.1016/0012-1606(66)90050-9) / DEVELOPMENTAL BIOLOGY (1966)
  52. TAUTZ, D, A NON-RADIOACTIVE INSITU HYBRIDIZATION METHOD FOR THE LOCALIZATION OF SPECIFIC RNAS IN DROSOPHILA EMBRYOS REVEALS TRANSLATIONAL CONTROL OF THE SEGMENTATION GENE HUNCHBACK, CHROMOSOMA 98: 81 (1989). (10.1007/BF00291041) / CHROMOSOMA (1989)
  53. TEPASS, U, PHENOTYPIC AND DEVELOPMENTAL ANALYSIS OF MUTATIONS AT THE CRUMBS-LOCUS, A GENE REQUIRED FOR THE DEVELOPMENT OF EPITHELIA IN DROSOPHILA-MELANOGASTER, ROUXS ARCHIVES OF DEVELOPMENTAL BIOLOGY 199: 189 (1990). (10.1007/BF01682078) / ROUXS ARCHIVES OF DEVELOPMENTAL BIOLOGY (1990)
  54. TRUMAN J.W. COMMUNICATION.
  55. TRUMAN, J.W., SPATIAL AND TEMPORAL PATTERNS OF NEUROGENESIS IN THE CENTRAL NERVOUS-SYSTEM OF DROSOPHILA-MELANOGASTER, DEVELOPMENTAL BIOLOGY 125: 145 (1988). (10.1016/0012-1606(88)90067-X) / DEVELOPMENTAL BIOLOGY (1988)
  56. Umansky S. R. Apoptosis: The Molecular Basis of Cell Death (1991).
  57. VAUX, D.L., BCL-2 GENE PROMOTES HEMATOPOIETIC-CELL SURVIVAL AND COOPERATES WITH C-MYC TO IMMORTALIZE PRE-B-CELLS, NATURE 335: 440 (1988). (10.1038/335440a0) / NATURE (1988)
  58. WHITE K unpublished data.
  59. WILLIAMS, G.T., MOLECULAR REGULATION OF APOPTOSIS - GENETIC-CONTROLS ON CELL-DEATH, CELL 74: 777 (1993). (10.1016/0092-8674(93)90457-2) / CELL (1993)
  60. WOLFF, T, CELL-DEATH IN NORMAL AND ROUGH EYE MUTANTS OF DROSOPHILA, DEVELOPMENT 113: 825 (1991). (10.1242/dev.113.3.825) / DEVELOPMENT (1991)
  61. Wurgler F. E. The Genetics and Biology of Drosophila 1C (1976).
  62. Yuan, J., Developmental Biology 138: 33 (1990). (10.1016/0012-1606(90)90174-H) / Developmental Biology (1990)
Dates
Type When
Created 18 years, 10 months ago (Oct. 5, 2006, 8:01 p.m.)
Deposited 1 year, 7 months ago (Jan. 15, 2024, 12:26 a.m.)
Indexed 3 weeks ago (Aug. 6, 2025, 9:09 a.m.)
Issued 31 years, 3 months ago (April 29, 1994)
Published 31 years, 3 months ago (April 29, 1994)
Published Print 31 years, 3 months ago (April 29, 1994)
Funders 0

None

@article{White_1994, title={Genetic Control of Programmed Cell Death in Drosophila}, volume={264}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.8171319}, DOI={10.1126/science.8171319}, number={5159}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={White, Kristin and Grether, Megan E. and Abrams, John M. and Young, Lynn and Farrell, Kim and Steller, Hermann}, year={1994}, month=apr, pages={677–683} }