Skip to main content
Genetics logoLink to Genetics
. 1995 Jan;139(1):309–320. doi: 10.1093/genetics/139.1.309

Signaling Activities of the Drosophila Wingless Gene Are Separately Mutable and Appear to Be Transduced at the Cell Surface

A Bejsovec 1, E Wieschaus 1
PMCID: PMC1206327  PMID: 7705631

Abstract

The Drosophila segment polarity gene wingless encodes an intercellular signaling molecule that transmits positional information during development of the embryonic epidermis. We have explored the mechanism of wg signal transduction by perturbing cellular processes genetically and by performing structure/function analysis of the Wg protein. We present evidence that Wingless protein may transduce signal at the cell surface and that Wg may bind to its cell surface receptor without necessarily activating it. We demonstrate that two specific signaling activities of the Wg molecule can be disrupted independently by mutation. Sequence analysis indicates that these different signaling activities are not promoted by discrete functional domains, but rather that the overall conformation of the molecule may control distinct signaling functions. We conclude that wg signaling may involve complex interactions between the Wg ligand and its cell surface receptor molecule(s) and that some of this complexity resides within the Wg ligand itself.

Full Text

The Full Text of this article is available as a PDF (7.0 MB).

Selected References

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

  1. Akam M. The molecular basis for metameric pattern in the Drosophila embryo. Development. 1987 Sep;101(1):1–22. [PubMed] [Google Scholar]
  2. Babu P. Early developmental subdivisions of the wing disk in Drosophila. Mol Gen Genet. 1977 Mar 16;151(3):289–294. doi: 10.1007/BF00268792. [DOI] [PubMed] [Google Scholar]
  3. Baker N. E. Embryonic and imaginal requirements for wingless, a segment-polarity gene in Drosophila. Dev Biol. 1988 Jan;125(1):96–108. doi: 10.1016/0012-1606(88)90062-0. [DOI] [PubMed] [Google Scholar]
  4. Baker N. E. Molecular cloning of sequences from wingless, a segment polarity gene in Drosophila: the spatial distribution of a transcript in embryos. EMBO J. 1987 Jun;6(6):1765–1773. doi: 10.1002/j.1460-2075.1987.tb02429.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bejsovec A., Wieschaus E. Segment polarity gene interactions modulate epidermal patterning in Drosophila embryos. Development. 1993 Oct;119(2):501–517. doi: 10.1242/dev.119.2.501. [DOI] [PubMed] [Google Scholar]
  6. Bradley R. S., Brown A. M. The proto-oncogene int-1 encodes a secreted protein associated with the extracellular matrix. EMBO J. 1990 May;9(5):1569–1575. doi: 10.1002/j.1460-2075.1990.tb08276.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cumberledge S., Krasnow M. A. Intercellular signalling in Drosophila segment formation reconstructed in vitro. Nature. 1993 Jun 10;363(6429):549–552. doi: 10.1038/363549a0. [DOI] [PubMed] [Google Scholar]
  8. Deuel T. F. Polypeptide growth factors: roles in normal and abnormal cell growth. Annu Rev Cell Biol. 1987;3:443–492. doi: 10.1146/annurev.cb.03.110187.002303. [DOI] [PubMed] [Google Scholar]
  9. DiNardo S., Kuner J. M., Theis J., O'Farrell P. H. Development of embryonic pattern in D. melanogaster as revealed by accumulation of the nuclear engrailed protein. Cell. 1985 Nov;43(1):59–69. doi: 10.1016/0092-8674(85)90012-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. DiNardo S., Sher E., Heemskerk-Jongens J., Kassis J. A., O'Farrell P. H. Two-tiered regulation of spatially patterned engrailed gene expression during Drosophila embryogenesis. Nature. 1988 Apr 14;332(6165):604–609. doi: 10.1038/332604a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Felder S., Miller K., Moehren G., Ullrich A., Schlessinger J., Hopkins C. R. Kinase activity controls the sorting of the epidermal growth factor receptor within the multivesicular body. Cell. 1990 May 18;61(4):623–634. doi: 10.1016/0092-8674(90)90474-s. [DOI] [PubMed] [Google Scholar]
  12. Foe V. E. Mitotic domains reveal early commitment of cells in Drosophila embryos. Development. 1989 Sep;107(1):1–22. [PubMed] [Google Scholar]
  13. González F., Swales L., Bejsovec A., Skaer H., Martinez Arias A. Secretion and movement of wingless protein in the epidermis of the Drosophila embryo. Mech Dev. 1991 Aug;35(1):43–54. doi: 10.1016/0925-4773(91)90040-d. [DOI] [PubMed] [Google Scholar]
  14. Heemskerk J., DiNardo S., Kostriken R., O'Farrell P. H. Multiple modes of engrailed regulation in the progression towards cell fate determination. Nature. 1991 Aug 1;352(6334):404–410. doi: 10.1038/352404a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hooper J. E., Scott M. P. The molecular genetic basis of positional information in insect segments. Results Probl Cell Differ. 1992;18:1–48. doi: 10.1007/978-3-540-47191-2_1. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Ingham P. W., Hidalgo A. Regulation of wingless transcription in the Drosophila embryo. Development. 1993 Jan;117(1):283–291. doi: 10.1242/dev.117.1.283. [DOI] [PubMed] [Google Scholar]
  18. Lohs-Schardin M., Cremer C., Nüsslein-Volhard C. A fate map for the larval epidermis of Drosophila melanogaster: localized cuticle defects following irradiation of the blastoderm with an ultraviolet laser microbeam. Dev Biol. 1979 Dec;73(2):239–255. doi: 10.1016/0012-1606(79)90065-4. [DOI] [PubMed] [Google Scholar]
  19. Martizez Arias A., Baker N. E., Ingham P. W. Role of segment polarity genes in the definition and maintenance of cell states in the Drosophila embryo. Development. 1988 May;103(1):157–170. doi: 10.1242/dev.103.1.157. [DOI] [PubMed] [Google Scholar]
  20. Miller J. B. Myoblast diversity in skeletal myogenesis: how much and to what end? Cell. 1992 Apr 3;69(1):1–3. doi: 10.1016/0092-8674(92)90111-o. [DOI] [PubMed] [Google Scholar]
  21. Nusse R., Varmus H. E. Wnt genes. Cell. 1992 Jun 26;69(7):1073–1087. doi: 10.1016/0092-8674(92)90630-u. [DOI] [PubMed] [Google Scholar]
  22. Nüsslein-Volhard C., Wieschaus E. Mutations affecting segment number and polarity in Drosophila. Nature. 1980 Oct 30;287(5785):795–801. doi: 10.1038/287795a0. [DOI] [PubMed] [Google Scholar]
  23. Papkoff J., Brown A. M., Varmus H. E. The int-1 proto-oncogene products are glycoproteins that appear to enter the secretory pathway. Mol Cell Biol. 1987 Nov;7(11):3978–3984. doi: 10.1128/mcb.7.11.3978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Papkoff J., Schryver B. Secreted int-1 protein is associated with the cell surface. Mol Cell Biol. 1990 Jun;10(6):2723–2730. doi: 10.1128/mcb.10.6.2723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Parkin N. T., Kitajewski J., Varmus H. E. Activity of Wnt-1 as a transmembrane protein. Genes Dev. 1993 Nov;7(11):2181–2193. doi: 10.1101/gad.7.11.2181. [DOI] [PubMed] [Google Scholar]
  26. Patel N. H., Martin-Blanco E., Coleman K. G., Poole S. J., Ellis M. C., Kornberg T. B., Goodman C. S. Expression of engrailed proteins in arthropods, annelids, and chordates. Cell. 1989 Sep 8;58(5):955–968. doi: 10.1016/0092-8674(89)90947-1. [DOI] [PubMed] [Google Scholar]
  27. Peifer M., Rauskolb C., Williams M., Riggleman B., Wieschaus E. The segment polarity gene armadillo interacts with the wingless signaling pathway in both embryonic and adult pattern formation. Development. 1991 Apr;111(4):1029–1043. doi: 10.1242/dev.111.4.1029. [DOI] [PubMed] [Google Scholar]
  28. Peifer M., Sweeton D., Casey M., Wieschaus E. wingless signal and Zeste-white 3 kinase trigger opposing changes in the intracellular distribution of Armadillo. Development. 1994 Feb;120(2):369–380. doi: 10.1242/dev.120.2.369. [DOI] [PubMed] [Google Scholar]
  29. Poodry C. A., Edgar L. Reversible alteration in the neuromuscular junctions of Drosophila melanogaster bearing a temperature-sensitive mutation, shibire. J Cell Biol. 1979 Jun;81(3):520–527. doi: 10.1083/jcb.81.3.520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Riggleman B., Schedl P., Wieschaus E. Spatial expression of the Drosophila segment polarity gene armadillo is posttranscriptionally regulated by wingless. Cell. 1990 Nov 2;63(3):549–560. doi: 10.1016/0092-8674(90)90451-j. [DOI] [PubMed] [Google Scholar]
  31. Rijsewijk F., Schuermann M., Wagenaar E., Parren P., Weigel D., Nusse R. The Drosophila homolog of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless. Cell. 1987 Aug 14;50(4):649–657. doi: 10.1016/0092-8674(87)90038-9. [DOI] [PubMed] [Google Scholar]
  32. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Tautz D., Pfeifle C. A non-radioactive in situ hybridization method for the localization of specific RNAs in Drosophila embryos reveals translational control of the segmentation gene hunchback. Chromosoma. 1989 Aug;98(2):81–85. doi: 10.1007/BF00291041. [DOI] [PubMed] [Google Scholar]
  34. Ullrich A., Schlessinger J. Signal transduction by receptors with tyrosine kinase activity. Cell. 1990 Apr 20;61(2):203–212. doi: 10.1016/0092-8674(90)90801-k. [DOI] [PubMed] [Google Scholar]
  35. van Ooyen A., Nusse R. Structure and nucleotide sequence of the putative mammary oncogene int-1; proviral insertions leave the protein-encoding domain intact. Cell. 1984 Nov;39(1):233–240. doi: 10.1016/0092-8674(84)90209-5. [DOI] [PubMed] [Google Scholar]
  36. van den Heuvel M., Nusse R., Johnston P., Lawrence P. A. Distribution of the wingless gene product in Drosophila embryos: a protein involved in cell-cell communication. Cell. 1989 Nov 17;59(4):739–749. doi: 10.1016/0092-8674(89)90020-2. [DOI] [PubMed] [Google Scholar]
  37. van der Bliek A. M., Meyerowitz E. M. Dynamin-like protein encoded by the Drosophila shibire gene associated with vesicular traffic. Nature. 1991 May 30;351(6325):411–414. doi: 10.1038/351411a0. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES