Skip to main content
Genetics logoLink to Genetics
. 1996 Sep;144(1):183–196. doi: 10.1093/genetics/144.1.183

Gutfeeling, a Drosophila Gene Encoding an Antizyme-like Protein, Is Required for Late Differentiation of Neurons and Muscles

A Salzberg 1, K Golden 1, R Bodmer 1, H J Bellen 1
PMCID: PMC1207492  PMID: 8878684

Abstract

The gutfeeling (guf) gene was uncovered in a genetic screen for genes that are required for proper development of the embryonic peripheral nervous system. Mutations in guf cause defects in growth cone guidance and fasciculation and loss of expression of several neuronal markers in the embryonic peripheral and central nervous systems. guf is required for terminal differentiation of neuronal cells. Mutations in guf also affect the development of muscles in the embryo. In the absence of guf activity, myoblasts are formed properly, but myoblast fusion and further differentiation of muscle fibers is severely impaired. The guf gene was cloned and found to encode a 21-kD protein with a significant sequence similarity to the mammalian ornithine decarboxylase antizyme (OAZ). In mammals, OAZ plays a key regulatory role in the polyamine biosynthetic pathway through its binding to, and inhibition of, ornithine decarboxylase (ODC), the first enzyme in the pathway. The elaborate regulation of ODC activity in mammals still lacks a defined developmental role and little is known about the involvement of polyamines in cellular differentiation. GUF is the first antizyme-like protein identified in invertebrates. We discuss its possible developmental roles in light of this homology.

Full Text

The Full Text of this article is available as a PDF (12.5 MB).

Selected References

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

  1. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  2. Arkhipova I. R. Promoter elements in Drosophila melanogaster revealed by sequence analysis. Genetics. 1995 Mar;139(3):1359–1369. doi: 10.1093/genetics/139.3.1359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bate M. The embryonic development of larval muscles in Drosophila. Development. 1990 Nov;110(3):791–804. doi: 10.1242/dev.110.3.791. [DOI] [PubMed] [Google Scholar]
  4. Bellen H. J., Kooyer S., D'Evelyn D., Pearlman J. The Drosophila couch potato protein is expressed in nuclei of peripheral neuronal precursors and shows homology to RNA-binding proteins. Genes Dev. 1992 Nov;6(11):2125–2136. doi: 10.1101/gad.6.11.2125. [DOI] [PubMed] [Google Scholar]
  5. Bier E., Vaessin H., Shepherd S., Lee K., McCall K., Barbel S., Ackerman L., Carretto R., Uemura T., Grell E. Searching for pattern and mutation in the Drosophila genome with a P-lacZ vector. Genes Dev. 1989 Sep;3(9):1273–1287. doi: 10.1101/gad.3.9.1273. [DOI] [PubMed] [Google Scholar]
  6. Bier E., Vaessin H., Younger-Shepherd S., Jan L. Y., Jan Y. N. deadpan, an essential pan-neural gene in Drosophila, encodes a helix-loop-helix protein similar to the hairy gene product. Genes Dev. 1992 Nov;6(11):2137–2151. doi: 10.1101/gad.6.11.2137. [DOI] [PubMed] [Google Scholar]
  7. Blochlinger K., Bodmer R., Jan L. Y., Jan Y. N. Patterns of expression of cut, a protein required for external sensory organ development in wild-type and cut mutant Drosophila embryos. Genes Dev. 1990 Aug;4(8):1322–1331. doi: 10.1101/gad.4.8.1322. [DOI] [PubMed] [Google Scholar]
  8. Bour B. A., O'Brien M. A., Lockwood W. L., Goldstein E. S., Bodmer R., Taghert P. H., Abmayr S. M., Nguyen H. T. Drosophila MEF2, a transcription factor that is essential for myogenesis. Genes Dev. 1995 Mar 15;9(6):730–741. doi: 10.1101/gad.9.6.730. [DOI] [PubMed] [Google Scholar]
  9. Campbell G., Göring H., Lin T., Spana E., Andersson S., Doe C. Q., Tomlinson A. RK2, a glial-specific homeodomain protein required for embryonic nerve cord condensation and viability in Drosophila. Development. 1994 Oct;120(10):2957–2966. doi: 10.1242/dev.120.10.2957. [DOI] [PubMed] [Google Scholar]
  10. Campos-Ortega J. A. Cellular interactions during early neurogenesis of Drosophila melanogaster. Trends Neurosci. 1988 Sep;11(9):400–405. doi: 10.1016/0166-2236(88)90077-x. [DOI] [PubMed] [Google Scholar]
  11. Coffino P., Poznanski A. Killer polyamines? J Cell Biochem. 1991 Jan;45(1):54–58. doi: 10.1002/jcb.240450112. [DOI] [PubMed] [Google Scholar]
  12. Constanti A., Galvan M. Fast inward-rectifying current accounts for anomalous rectification in olfactory cortex neurones. J Physiol. 1983 Feb;335:153–178. doi: 10.1113/jphysiol.1983.sp014526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Corbin V., Michelson A. M., Abmayr S. M., Neel V., Alcamo E., Maniatis T., Young M. W. A role for the Drosophila neurogenic genes in mesoderm differentiation. Cell. 1991 Oct 18;67(2):311–323. doi: 10.1016/0092-8674(91)90183-y. [DOI] [PubMed] [Google Scholar]
  14. Ficker E., Taglialatela M., Wible B. A., Henley C. M., Brown A. M. Spermine and spermidine as gating molecules for inward rectifier K+ channels. Science. 1994 Nov 11;266(5187):1068–1072. doi: 10.1126/science.7973666. [DOI] [PubMed] [Google Scholar]
  15. Fujita S. C., Zipursky S. L., Benzer S., Ferrús A., Shotwell S. L. Monoclonal antibodies against the Drosophila nervous system. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7929–7933. doi: 10.1073/pnas.79.24.7929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ghysen A., Dambly-Chaudière C., Jan L. Y., Jan Y. N. Cell interactions and gene interactions in peripheral neurogenesis. Genes Dev. 1993 May;7(5):723–733. doi: 10.1101/gad.7.5.723. [DOI] [PubMed] [Google Scholar]
  17. Goodman C. S., Bastiani M. J., Doe C. Q., du Lac S., Helfand S. L., Kuwada J. Y., Thomas J. B. Cell recognition during neuronal development. Science. 1984 Sep 21;225(4668):1271–1279. doi: 10.1126/science.6474176. [DOI] [PubMed] [Google Scholar]
  18. Guo M., Bier E., Jan L. Y., Jan Y. N. tramtrack acts downstream of numb to specify distinct daughter cell fates during asymmetric cell divisions in the Drosophila PNS. Neuron. 1995 May;14(5):913–925. doi: 10.1016/0896-6273(95)90330-5. [DOI] [PubMed] [Google Scholar]
  19. Halter D. A., Urban J., Rickert C., Ner S. S., Ito K., Travers A. A., Technau G. M. The homeobox gene repo is required for the differentiation and maintenance of glia function in the embryonic nervous system of Drosophila melanogaster. Development. 1995 Feb;121(2):317–332. doi: 10.1242/dev.121.2.317. [DOI] [PubMed] [Google Scholar]
  20. Heby O. Role of polyamines in the control of cell proliferation and differentiation. Differentiation. 1981;19(1):1–20. doi: 10.1111/j.1432-0436.1981.tb01123.x. [DOI] [PubMed] [Google Scholar]
  21. Hortsch M., Patel N. H., Bieber A. J., Traquina Z. R., Goodman C. S. Drosophila neurotactin, a surface glycoprotein with homology to serine esterases, is dynamically expressed during embryogenesis. Development. 1990 Dec;110(4):1327–1340. doi: 10.1242/dev.110.4.1327. [DOI] [PubMed] [Google Scholar]
  22. Hoshizaki D. K., Blackburn T., Price C., Ghosh M., Miles K., Ragucci M., Sweis R. Embryonic fat-cell lineage in Drosophila melanogaster. Development. 1994 Sep;120(9):2489–2499. doi: 10.1242/dev.120.9.2489. [DOI] [PubMed] [Google Scholar]
  23. Ichiba T., Matsufuji S., Miyazaki Y., Murakami Y., Tanaka K., Ichihara A., Hayashi S. Functional regions of ornithine decarboxylase antizyme. Biochem Biophys Res Commun. 1994 May 16;200(3):1721–1727. doi: 10.1006/bbrc.1994.1651. [DOI] [PubMed] [Google Scholar]
  24. Ingham P. W., Taylor A. M., Nakano Y. Role of the Drosophila patched gene in positional signalling. Nature. 1991 Sep 12;353(6340):184–187. doi: 10.1038/353184a0. [DOI] [PubMed] [Google Scholar]
  25. Jan Y. N., Jan L. Y. HLH proteins, fly neurogenesis, and vertebrate myogenesis. Cell. 1993 Dec 3;75(5):827–830. doi: 10.1016/0092-8674(93)90525-u. [DOI] [PubMed] [Google Scholar]
  26. Jarman A. P., Grell E. H., Ackerman L., Jan L. Y., Jan Y. N. Atonal is the proneural gene for Drosophila photoreceptors. Nature. 1994 Jun 2;369(6479):398–400. doi: 10.1038/369398a0. [DOI] [PubMed] [Google Scholar]
  27. Kania A., Han P. L., Kim Y. T., Bellen H. Neuromusculin, a Drosophila gene expressed in peripheral neuronal precursors and muscles, encodes a cell adhesion molecule. Neuron. 1993 Oct;11(4):673–687. doi: 10.1016/0896-6273(93)90078-6. [DOI] [PubMed] [Google Scholar]
  28. Kania A., Salzberg A., Bhat M., D'Evelyn D., He Y., Kiss I., Bellen H. J. P-element mutations affecting embryonic peripheral nervous system development in Drosophila melanogaster. Genetics. 1995 Apr;139(4):1663–1678. doi: 10.1093/genetics/139.4.1663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kiehart D. P., Feghali R. Cytoplasmic myosin from Drosophila melanogaster. J Cell Biol. 1986 Oct;103(4):1517–1525. doi: 10.1083/jcb.103.4.1517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lilly B., Zhao B., Ranganayakulu G., Paterson B. M., Schulz R. A., Olson E. N. Requirement of MADS domain transcription factor D-MEF2 for muscle formation in Drosophila. Science. 1995 Feb 3;267(5198):688–693. doi: 10.1126/science.7839146. [DOI] [PubMed] [Google Scholar]
  31. Littleton J. T., Bellen H. J., Perin M. S. Expression of synaptotagmin in Drosophila reveals transport and localization of synaptic vesicles to the synapse. Development. 1993 Aug;118(4):1077–1088. doi: 10.1242/dev.118.4.1077. [DOI] [PubMed] [Google Scholar]
  32. Lopatin A. N., Makhina E. N., Nichols C. G. Potassium channel block by cytoplasmic polyamines as the mechanism of intrinsic rectification. Nature. 1994 Nov 24;372(6504):366–369. doi: 10.1038/372366a0. [DOI] [PubMed] [Google Scholar]
  33. Löwkvist B., Emanuelsson H., Egyházi E., Sjöberg J., Långström E., Heby O. Transcriptional inhibition in early chick embryos as a result of polyamine depletion. Dev Biol. 1986 Aug;116(2):291–301. doi: 10.1016/0012-1606(86)90132-6. [DOI] [PubMed] [Google Scholar]
  34. Macrae M., Plasterk R. H., Coffino P. The ornithine decarboxylase gene of Caenorhabditis elegans: cloning, mapping and mutagenesis. Genetics. 1995 Jun;140(2):517–525. doi: 10.1093/genetics/140.2.517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Mamroud-Kidron E., Omer-Itsicovich M., Bercovich Z., Tobias K. E., Rom E., Kahana C. A unified pathway for the degradation of ornithine decarboxylase in reticulocyte lysate requires interaction with the polyamine-induced protein, ornithine decarboxylase antizyme. Eur J Biochem. 1994 Dec 1;226(2):547–554. doi: 10.1111/j.1432-1033.1994.tb20079.x. [DOI] [PubMed] [Google Scholar]
  36. Matsufuji S., Matsufuji T., Miyazaki Y., Murakami Y., Atkins J. F., Gesteland R. F., Hayashi S. Autoregulatory frameshifting in decoding mammalian ornithine decarboxylase antizyme. Cell. 1995 Jan 13;80(1):51–60. doi: 10.1016/0092-8674(95)90450-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Michelson A. M., Abmayr S. M., Bate M., Arias A. M., Maniatis T. Expression of a MyoD family member prefigures muscle pattern in Drosophila embryos. Genes Dev. 1990 Dec;4(12A):2086–2097. doi: 10.1101/gad.4.12a.2086. [DOI] [PubMed] [Google Scholar]
  38. Mitchell J. L., Judd G. G., Bareyal-Leyser A., Ling S. Y. Feedback repression of polyamine transport is mediated by antizyme in mammalian tissue-culture cells. Biochem J. 1994 Apr 1;299(Pt 1):19–22. doi: 10.1042/bj2990019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Miyazaki Y., Matsufuji S., Hayashi S. Cloning and characterization of a rat gene encoding ornithine decarboxylase antizyme. Gene. 1992 Apr 15;113(2):191–197. doi: 10.1016/0378-1119(92)90395-6. [DOI] [PubMed] [Google Scholar]
  40. Murakami Y., Tanaka K., Matsufuji S., Miyazaki Y., Hayashi S. Antizyme, a protein induced by polyamines, accelerates the degradation of ornithine decarboxylase in Chinese-hamster ovary-cell extracts. Biochem J. 1992 May 1;283(Pt 3):661–664. doi: 10.1042/bj2830661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Nye J. S., Kopan R., Axel R. An activated Notch suppresses neurogenesis and myogenesis but not gliogenesis in mammalian cells. Development. 1994 Sep;120(9):2421–2430. doi: 10.1242/dev.120.9.2421. [DOI] [PubMed] [Google Scholar]
  42. Rao Y., Vaessin H., Jan L. Y., Jan Y. N. Neuroectoderm in Drosophila embryos is dependent on the mesoderm for positioning but not for formation. Genes Dev. 1991 Sep;5(9):1577–1588. doi: 10.1101/gad.5.9.1577. [DOI] [PubMed] [Google Scholar]
  43. Rom E., Kahana C. Isolation and characterization of the Drosophila ornithine decarboxylase locus: evidence for the presence of two transcribed ODC genes in the Drosophila genome. DNA Cell Biol. 1993 Jul-Aug;12(6):499–508. doi: 10.1089/dna.1993.12.499. [DOI] [PubMed] [Google Scholar]
  44. Sakmann B., Trube G. Conductance properties of single inwardly rectifying potassium channels in ventricular cells from guinea-pig heart. J Physiol. 1984 Feb;347:641–657. doi: 10.1113/jphysiol.1984.sp015088. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Salzberg A., D'Evelyn D., Schulze K. L., Lee J. K., Strumpf D., Tsai L., Bellen H. J. Mutations affecting the pattern of the PNS in Drosophila reveal novel aspects of neuronal development. Neuron. 1994 Aug;13(2):269–287. doi: 10.1016/0896-6273(94)90346-8. [DOI] [PubMed] [Google Scholar]
  46. Slesinger P. A., Patil N., Liao Y. J., Jan Y. N., Jan L. Y., Cox D. R. Functional effects of the mouse weaver mutation on G protein-gated inwardly rectifying K+ channels. Neuron. 1996 Feb;16(2):321–331. doi: 10.1016/s0896-6273(00)80050-1. [DOI] [PubMed] [Google Scholar]
  47. Suzuki T., He Y., Kashiwagi K., Murakami Y., Hayashi S., Igarashi K. Antizyme protects against abnormal accumulation and toxicity of polyamines in ornithine decarboxylase-overproducing cells. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8930–8934. doi: 10.1073/pnas.91.19.8930. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Tabor C. W., Tabor H. Polyamines. Annu Rev Biochem. 1984;53:749–790. doi: 10.1146/annurev.bi.53.070184.003533. [DOI] [PubMed] [Google Scholar]
  49. Török T., Tick G., Alvarado M., Kiss I. P-lacW insertional mutagenesis on the second chromosome of Drosophila melanogaster: isolation of lethals with different overgrowth phenotypes. Genetics. 1993 Sep;135(1):71–80. doi: 10.1093/genetics/135.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Uemura T., Shepherd S., Ackerman L., Jan L. Y., Jan Y. N. numb, a gene required in determination of cell fate during sensory organ formation in Drosophila embryos. Cell. 1989 Jul 28;58(2):349–360. doi: 10.1016/0092-8674(89)90849-0. [DOI] [PubMed] [Google Scholar]
  51. Vactor D. V., Sink H., Fambrough D., Tsoo R., Goodman C. S. Genes that control neuromuscular specificity in Drosophila. Cell. 1993 Jun 18;73(6):1137–1153. doi: 10.1016/0092-8674(93)90643-5. [DOI] [PubMed] [Google Scholar]
  52. Vaessin H., Grell E., Wolff E., Bier E., Jan L. Y., Jan Y. N. prospero is expressed in neuronal precursors and encodes a nuclear protein that is involved in the control of axonal outgrowth in Drosophila. Cell. 1991 Nov 29;67(5):941–953. doi: 10.1016/0092-8674(91)90367-8. [DOI] [PubMed] [Google Scholar]
  53. Volk T. A new member of the spectrin superfamily may participate in the formation of embryonic muscle attachments in Drosophila. Development. 1992 Nov;116(3):721–730. doi: 10.1242/dev.116.3.721. [DOI] [PubMed] [Google Scholar]
  54. Wilson C., Pearson R. K., Bellen H. J., O'Kane C. J., Grossniklaus U., Gehring W. J. P-element-mediated enhancer detection: an efficient method for isolating and characterizing developmentally regulated genes in Drosophila. Genes Dev. 1989 Sep;3(9):1301–1313. doi: 10.1101/gad.3.9.1301. [DOI] [PubMed] [Google Scholar]
  55. Zinn K., McAllister L., Goodman C. S. Sequence analysis and neuronal expression of fasciclin I in grasshopper and Drosophila. Cell. 1988 May 20;53(4):577–587. doi: 10.1016/0092-8674(88)90574-0. [DOI] [PubMed] [Google Scholar]
  56. de la Escalera S., Bockamp E. O., Moya F., Piovant M., Jiménez F. Characterization and gene cloning of neurotactin, a Drosophila transmembrane protein related to cholinesterases. EMBO J. 1990 Nov;9(11):3593–3601. doi: 10.1002/j.1460-2075.1990.tb07570.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES