Skip to main content
PMC home page
Genetics logoLink to Genetics
. 2003 Jul;164(3):989–1001. doi: 10.1093/genetics/164.3.989

Regulation of maternal transcript destabilization during egg activation in Drosophila.

Wael Tadros 1, Simon A Houston 1, Arash Bashirullah 1, Ramona L Cooperstock 1, Jennifer L Semotok 1, Bruce H Reed 1, Howard D Lipshitz 1
PMCID: PMC1462612  PMID: 12871909

Abstract

In animals, the transfer of developmental control from maternal RNAs and proteins to zygotically derived products occurs at the midblastula transition. This is accompanied by the destabilization of a subset of maternal transcripts. In Drosophila, maternal transcript destabilization occurs in the absence of fertilization and requires specific cis-acting instability elements. We show here that egg activation is necessary and sufficient to trigger transcript destabilization. We have identified 13 maternal-effect lethal loci that, when mutated, result in failure of maternal transcript degradation. All mutants identified are defective in one or more additional processes associated with egg activation. These include vitelline membrane reorganization, cortical microtubule depolymerization, translation of maternal mRNA, completion of meiosis, and chromosome condensation (the S-to-M transition) after meiosis. The least pleiotropic class of transcript destabilization mutants consists of three genes: pan gu, plutonium, and giant nuclei. These three genes regulate the S-to-M transition at the end of meiosis and are thought to be required for the maintenance of cyclin-dependent kinase (CDK) activity during this cell cycle transition. Consistent with a possible functional connection between this S-to-M transition and transcript destabilization, we show that in vitro-activated eggs, which exhibit aberrant postmeiotic chromosome condensation, fail to initiate transcript degradation. Several genetic tests exclude the possibility that reduction of CDK/cyclin complex activity per se is responsible for the failure to trigger transcript destabilization in these mutants. We propose that the trigger for transcript destabilization occurs coincidently with the S-to-M transition at the end of meiosis and that pan gu, plutonium, and giant nuclei regulate maternal transcript destabilization independent of their role in cell cycle regulation.

Full Text

The Full Text of this article is available as a PDF (372.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alphey L., Jimenez J., White-Cooper H., Dawson I., Nurse P., Glover D. M. twine, a cdc25 homolog that functions in the male and female germline of Drosophila. Cell. 1992 Jun 12;69(6):977–988. doi: 10.1016/0092-8674(92)90616-k. [DOI] [PubMed] [Google Scholar]
  2. Anderson K. V., Lengyel J. A. Rates of synthesis of major classes of RNA in Drosophila embryos. Dev Biol. 1979 May;70(1):217–231. doi: 10.1016/0012-1606(79)90018-6. [DOI] [PubMed] [Google Scholar]
  3. Axton J. M., Shamanski F. L., Young L. M., Henderson D. S., Boyd J. B., Orr-Weaver T. L. The inhibitor of DNA replication encoded by the Drosophila gene plutonium is a small, ankyrin repeat protein. EMBO J. 1994 Jan 15;13(2):462–470. doi: 10.1002/j.1460-2075.1994.tb06281.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bashirullah A., Cooperstock R. L., Lipshitz H. D. Spatial and temporal control of RNA stability. Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7025–7028. doi: 10.1073/pnas.111145698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bashirullah A., Halsell S. R., Cooperstock R. L., Kloc M., Karaiskakis A., Fisher W. W., Fu W., Hamilton J. K., Etkin L. D., Lipshitz H. D. Joint action of two RNA degradation pathways controls the timing of maternal transcript elimination at the midblastula transition in Drosophila melanogaster. EMBO J. 1999 May 4;18(9):2610–2620. doi: 10.1093/emboj/18.9.2610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Berry L. D., Gould K. L. Regulation of Cdc2 activity by phosphorylation at T14/Y15. Prog Cell Cycle Res. 1996;2:99–105. doi: 10.1007/978-1-4615-5873-6_10. [DOI] [PubMed] [Google Scholar]
  7. Brent A. E., MacQueen A., Hazelrigg T. The Drosophila wispy gene is required for RNA localization and other microtubule-based events of meiosis and early embryogenesis. Genetics. 2000 Apr;154(4):1649–1662. doi: 10.1093/genetics/154.4.1649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brunet-Simon A., Henrion G., Renard J. P., Duranthon V. Onset of zygotic transcription and maternal transcript legacy in the rabbit embryo. Mol Reprod Dev. 2001 Feb;58(2):127–136. doi: 10.1002/1098-2795(200102)58:2<127::AID-MRD1>3.0.CO;2-A. [DOI] [PubMed] [Google Scholar]
  9. Chu D. T., Klymkowsky M. W. The appearance of acetylated alpha-tubulin during early development and cellular differentiation in Xenopus. Dev Biol. 1989 Nov;136(1):104–117. doi: 10.1016/0012-1606(89)90134-6. [DOI] [PubMed] [Google Scholar]
  10. Courtot C., Fankhauser C., Simanis V., Lehner C. F. The Drosophila cdc25 homolog twine is required for meiosis. Development. 1992 Oct;116(2):405–416. doi: 10.1242/dev.116.2.405. [DOI] [PubMed] [Google Scholar]
  11. Dawson I. A., Roth S., Akam M., Artavanis-Tsakonas S. Mutations of the fizzy locus cause metaphase arrest in Drosophila melanogaster embryos. Development. 1993 Jan;117(1):359–376. doi: 10.1242/dev.117.1.359. [DOI] [PubMed] [Google Scholar]
  12. Degelmann A., Hardy P. A., Mahowald A. P. Genetic analysis of two female-sterile loci affecting eggshell integrity and embryonic pattern formation in Drosophila melanogaster. Genetics. 1990 Oct;126(2):427–434. doi: 10.1093/genetics/126.2.427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ding D., Parkhurst S. M., Halsell S. R., Lipshitz H. D. Dynamic Hsp83 RNA localization during Drosophila oogenesis and embryogenesis. Mol Cell Biol. 1993 Jun;13(6):3773–3781. doi: 10.1128/mcb.13.6.3773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dorée M., Galas S. The cyclin-dependent protein kinases and the control of cell division. FASEB J. 1994 Nov;8(14):1114–1121. doi: 10.1096/fasebj.8.14.7958616. [DOI] [PubMed] [Google Scholar]
  15. Driever W., Nüsslein-Volhard C. A gradient of bicoid protein in Drosophila embryos. Cell. 1988 Jul 1;54(1):83–93. doi: 10.1016/0092-8674(88)90182-1. [DOI] [PubMed] [Google Scholar]
  16. Duval C., Bouvet P., Omilli F., Roghi C., Dorel C., LeGuellec R., Paris J., Osborne H. B. Stability of maternal mRNA in Xenopus embryos: role of transcription and translation. Mol Cell Biol. 1990 Aug;10(8):4123–4129. doi: 10.1128/mcb.10.8.4123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Edgar B. A., Datar S. A. Zygotic degradation of two maternal Cdc25 mRNAs terminates Drosophila's early cell cycle program. Genes Dev. 1996 Aug 1;10(15):1966–1977. doi: 10.1101/gad.10.15.1966. [DOI] [PubMed] [Google Scholar]
  18. Edgar B. A., Odell G. M., Schubiger G. A genetic switch, based on negative regulation, sharpens stripes in Drosophila embryos. Dev Genet. 1989;10(3):124–142. doi: 10.1002/dvg.1020100303. [DOI] [PubMed] [Google Scholar]
  19. Endow S. A., Komma D. J. Spindle dynamics during meiosis in Drosophila oocytes. J Cell Biol. 1997 Jun 16;137(6):1321–1336. doi: 10.1083/jcb.137.6.1321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Fenger D. D., Carminati J. L., Burney-Sigman D. L., Kashevsky H., Dines J. L., Elfring L. K., Orr-Weaver T. L. PAN GU: a protein kinase that inhibits S phase and promotes mitosis in early Drosophila development. Development. 2000 Nov;127(22):4763–4774. doi: 10.1242/dev.127.22.4763. [DOI] [PubMed] [Google Scholar]
  21. Freeman M., Nüsslein-Volhard C., Glover D. M. The dissociation of nuclear and centrosomal division in gnu, a mutation causing giant nuclei in Drosophila. Cell. 1986 Aug 1;46(3):457–468. doi: 10.1016/0092-8674(86)90666-5. [DOI] [PubMed] [Google Scholar]
  22. Gamberi Chiara, Peterson David S., He Luming, Gottlieb Ellen. An anterior function for the Drosophila posterior determinant Pumilio. Development. 2002 Jun;129(11):2699–2710. doi: 10.1242/dev.129.11.2699. [DOI] [PubMed] [Google Scholar]
  23. Gay N. J., Keith F. J. Regulation of translation and proteolysis during the development of embryonic dorso-ventral polarity in Drosophila. Homology of easter proteinase with Limulus proclotting enzyme and translational activation of Toll receptor synthesis. Biochim Biophys Acta. 1992 Oct 20;1132(3):290–296. doi: 10.1016/0167-4781(92)90163-t. [DOI] [PubMed] [Google Scholar]
  24. Groisman I., Huang Y. S., Mendez R., Cao Q., Theurkauf W., Richter J. D. CPEB, maskin, and cyclin B1 mRNA at the mitotic apparatus: implications for local translational control of cell division. Cell. 2000 Oct 27;103(3):435–447. doi: 10.1016/s0092-8674(00)00135-5. [DOI] [PubMed] [Google Scholar]
  25. Heifetz Y., Lung O., Frongillo E. A., Jr, Wolfner M. F. The Drosophila seminal fluid protein Acp26Aa stimulates release of oocytes by the ovary. Curr Biol. 2000 Jan 27;10(2):99–102. doi: 10.1016/s0960-9822(00)00288-8. [DOI] [PubMed] [Google Scholar]
  26. Heifetz Y., Yu J., Wolfner M. F. Ovulation triggers activation of Drosophila oocytes. Dev Biol. 2001 Jun 15;234(2):416–424. doi: 10.1006/dbio.2001.0246. [DOI] [PubMed] [Google Scholar]
  27. Henrion G., Brunet A., Renard J. P., Duranthon V. Identification of maternal transcripts that progressively disappear during the cleavage period of rabbit embryos. Mol Reprod Dev. 1997 Aug;47(4):353–362. doi: 10.1002/(SICI)1098-2795(199708)47:4<353::AID-MRD1>3.0.CO;2-J. [DOI] [PubMed] [Google Scholar]
  28. Henrion G., Renard J. P., Chesné P., Oudin J. F., Maniey D., Brunet A., Osborne H. B., Duranthon V. Differential regulation of the translation and the stability of two maternal transcripts in preimplantation rabbit embryos. Mol Reprod Dev. 2000 May;56(1):12–25. doi: 10.1002/(SICI)1098-2795(200005)56:1<12::AID-MRD3>3.0.CO;2-#. [DOI] [PubMed] [Google Scholar]
  29. Hong C. C., Hashimoto C. An unusual mosaic protein with a protease domain, encoded by the nudel gene, is involved in defining embryonic dorsoventral polarity in Drosophila. Cell. 1995 Sep 8;82(5):785–794. doi: 10.1016/0092-8674(95)90475-1. [DOI] [PubMed] [Google Scholar]
  30. Jiménez Gerardo, González-Reyes Acaimo, Casanova Jordi. Cell surface proteins Nasrat and Polehole stabilize the Torso-like extracellular determinant in Drosophila oogenesis. Genes Dev. 2002 Apr 15;16(8):913–918. doi: 10.1101/gad.223902. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kishida M., Callard G. V. Distinct cytochrome P450 aromatase isoforms in zebrafish (Danio rerio) brain and ovary are differentially programmed and estrogen regulated during early development. Endocrinology. 2001 Feb;142(2):740–750. doi: 10.1210/endo.142.2.7928. [DOI] [PubMed] [Google Scholar]
  32. LeMosy E. K., Hashimoto C. The nudel protease of Drosophila is required for eggshell biogenesis in addition to embryonic patterning. Dev Biol. 2000 Jan 15;217(2):352–361. doi: 10.1006/dbio.1999.9562. [DOI] [PubMed] [Google Scholar]
  33. LeMosy E. K., Kemler D., Hashimoto C. Role of Nudel protease activation in triggering dorsoventral polarization of the Drosophila embryo. Development. 1998 Oct;125(20):4045–4053. doi: 10.1242/dev.125.20.4045. [DOI] [PubMed] [Google Scholar]
  34. LeMosy E. K., Leclerc C. L., Hashimoto C. Biochemical defects of mutant nudel alleles causing early developmental arrest or dorsalization of the Drosophila embryo. Genetics. 2000 Jan;154(1):247–257. doi: 10.1093/genetics/154.1.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Lee L. A., Elfring L. K., Bosco G., Orr-Weaver T. L. A genetic screen for suppressors and enhancers of the Drosophila PAN GU cell cycle kinase identifies cyclin B as a target. Genetics. 2001 Aug;158(4):1545–1556. doi: 10.1093/genetics/158.4.1545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Lieberfarb M. E., Chu T., Wreden C., Theurkauf W., Gergen J. P., Strickland S. Mutations that perturb poly(A)-dependent maternal mRNA activation block the initiation of development. Development. 1996 Feb;122(2):579–588. doi: 10.1242/dev.122.2.579. [DOI] [PubMed] [Google Scholar]
  37. Lin H. F., Wolfner M. F. The Drosophila maternal-effect gene fs(1)Ya encodes a cell cycle-dependent nuclear envelope component required for embryonic mitosis. Cell. 1991 Jan 11;64(1):49–62. doi: 10.1016/0092-8674(91)90208-g. [DOI] [PubMed] [Google Scholar]
  38. Liu J., Lin H., Lopez J. M., Wolfner M. F. Formation of the male pronuclear lamina in Drosophila melanogaster. Dev Biol. 1997 Apr 15;184(2):187–196. doi: 10.1006/dbio.1997.8523. [DOI] [PubMed] [Google Scholar]
  39. Liu J., Song K., Wolfner M. F. Mutational analyses of fs(1)Ya, an essential, developmentally regulated, nuclear envelope protein in Drosophila. Genetics. 1995 Dec;141(4):1473–1481. doi: 10.1093/genetics/141.4.1473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Lopez J. M., Song K., Hirshfeld A. B., Lin H., Wolfner M. F. The Drosophila fs(1)Ya protein, which is needed for the first mitotic division, is in the nuclear lamina and in the envelopes of cleavage nuclei, pronuclei, and nonmitotic nuclei. Dev Biol. 1994 May;163(1):202–211. doi: 10.1006/dbio.1994.1136. [DOI] [PubMed] [Google Scholar]
  41. Mahowald A. P., Goralski T. J., Caulton J. H. In vitro activation of Drosophila eggs. Dev Biol. 1983 Aug;98(2):437–445. doi: 10.1016/0012-1606(83)90373-1. [DOI] [PubMed] [Google Scholar]
  42. Page A. W., Orr-Weaver T. L. Activation of the meiotic divisions in Drosophila oocytes. Dev Biol. 1997 Mar 15;183(2):195–207. doi: 10.1006/dbio.1997.8506. [DOI] [PubMed] [Google Scholar]
  43. Page A. W., Orr-Weaver T. L. The Drosophila genes grauzone and cortex are necessary for proper female meiosis. J Cell Sci. 1996 Jul;109(Pt 7):1707–1715. doi: 10.1242/jcs.109.7.1707. [DOI] [PubMed] [Google Scholar]
  44. Sallés F. J., Lieberfarb M. E., Wreden C., Gergen J. P., Strickland S. Coordinate initiation of Drosophila development by regulated polyadenylation of maternal messenger RNAs. Science. 1994 Dec 23;266(5193):1996–1999. doi: 10.1126/science.7801127. [DOI] [PubMed] [Google Scholar]
  45. Sallés F. J., Lieberfarb M. E., Wreden C., Gergen J. P., Strickland S. Coordinate initiation of Drosophila development by regulated polyadenylation of maternal messenger RNAs. Science. 1994 Dec 23;266(5193):1996–1999. doi: 10.1126/science.7801127. [DOI] [PubMed] [Google Scholar]
  46. Savant S. S., Waring G. L. Molecular analysis and rescue of a vitelline membrane mutant in Drosophila. Dev Biol. 1989 Sep;135(1):43–52. doi: 10.1016/0012-1606(89)90156-5. [DOI] [PubMed] [Google Scholar]
  47. Schüpbach T., Wieschaus E. Female sterile mutations on the second chromosome of Drosophila melanogaster. I. Maternal effect mutations. Genetics. 1989 Jan;121(1):101–117. doi: 10.1093/genetics/121.1.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Shamanski F. L., Orr-Weaver T. L. The Drosophila plutonium and pan gu genes regulate entry into S phase at fertilization. Cell. 1991 Sep 20;66(6):1289–1300. doi: 10.1016/0092-8674(91)90050-9. [DOI] [PubMed] [Google Scholar]
  49. Smibert C. A., Wilson J. E., Kerr K., Macdonald P. M. smaug protein represses translation of unlocalized nanos mRNA in the Drosophila embryo. Genes Dev. 1996 Oct 15;10(20):2600–2609. doi: 10.1101/gad.10.20.2600. [DOI] [PubMed] [Google Scholar]
  50. Stern B., Ried G., Clegg N. J., Grigliatti T. A., Lehner C. F. Genetic analysis of the Drosophila cdc2 homolog. Development. 1993 Jan;117(1):219–232. doi: 10.1242/dev.117.1.219. [DOI] [PubMed] [Google Scholar]
  51. Swan A., Hijal S., Hilfiker A., Suter B. Identification of new X-chromosomal genes required for Drosophila oogenesis and novel roles for fs(1)Yb, brainiac and dunce. Genome Res. 2001 Jan;11(1):67–77. doi: 10.1101/gr.156001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Swan W. D. SPLEEN THERAPY IN TUBERCULOSIS. Can Med Assoc J. 1930 Jan;22(1):33–34. [PMC free article] [PubMed] [Google Scholar]
  53. Theurkauf W. E. Microtubules and cytoplasm organization during Drosophila oogenesis. Dev Biol. 1994 Oct;165(2):352–360. doi: 10.1006/dbio.1994.1258. [DOI] [PubMed] [Google Scholar]
  54. Theurkauf W. E., Smiley S., Wong M. L., Alberts B. M. Reorganization of the cytoskeleton during Drosophila oogenesis: implications for axis specification and intercellular transport. Development. 1992 Aug;115(4):923–936. doi: 10.1242/dev.115.4.923. [DOI] [PubMed] [Google Scholar]
  55. Waring G. L. Morphogenesis of the eggshell in Drosophila. Int Rev Cytol. 2000;198:67–108. doi: 10.1016/s0074-7696(00)98003-3. [DOI] [PubMed] [Google Scholar]
  56. White-Cooper H., Alphey L., Glover D. M. The cdc25 homologue twine is required for only some aspects of the entry into meiosis in Drosophila. J Cell Sci. 1993 Dec;106(Pt 4):1035–1044. doi: 10.1242/jcs.106.4.1035. [DOI] [PubMed] [Google Scholar]
  57. Yu Jing, Wolfner Mariana F. The Drosophila nuclear lamina protein YA binds to DNA and histone H2B with four domains. Mol Biol Cell. 2002 Feb;13(2):558–569. doi: 10.1091/mbc.01-07-0336. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES