Skip to main content
PMC home page
Genetics logoLink to Genetics
. 1995 Aug;140(4):1339–1352. doi: 10.1093/genetics/140.4.1339

A Screen for Modifiers of Deformed Function in Drosophila

K W Harding 1, G Gellon 1, N McGinnis 1, W McGinnis 1
PMCID: PMC1206698  PMID: 7498774

Abstract

Proteins produced by the homeotic genes of the Hox family assign different identities to cells on the anterior/posterior axis. Relatively little is known about the signalling pathways that modulate their activities or the factors with which they interact to assign specific segmental identities. To identify genes that might encode such functions, we performed a screen for second site mutations that reduce the viability of animals carrying hypomorphic mutant alleles of the Drosophila homeotic locus, Deformed. Genes mapping to six complementation groups on the third chromosome were isolated as modifiers of Deformed function. Products of two of these genes, sallimus and moira, have been previously proposed as homeotic activators since they suppress the dominant adult phenotype of Polycomb mutants. Mutations in hedgehog, which encodes secreted signalling proteins, were also isolated as Deformed loss-of-function enhancers. Hedgehog mutant alleles also suppress the Polycomb phenotype. Mutations were also isolated in a few genes that interact with Deformed but not with Polycomb, indicating that the screen identified genes that are not general homeotic activators. Two of these genes, cap `n' collar and defaced, have defects in embryonic head development that are similar to defects seen in loss of function Deformed mutants.

Full Text

The Full Text of this article is available as a PDF (4.8 MB).

Selected References

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

  1. Affolter M., Schier A., Gehring W. J. Homeodomain proteins and the regulation of gene expression. Curr Opin Cell Biol. 1990 Jun;2(3):485–495. doi: 10.1016/0955-0674(90)90132-x. [DOI] [PubMed] [Google Scholar]
  2. Bender W., Akam M., Karch F., Beachy P. A., Peifer M., Spierer P., Lewis E. B., Hogness D. S. Molecular Genetics of the Bithorax Complex in Drosophila melanogaster. Science. 1983 Jul 1;221(4605):23–29. doi: 10.1126/science.221.4605.23. [DOI] [PubMed] [Google Scholar]
  3. Botas J. Control of morphogenesis and differentiation by HOM/Hox genes. Curr Opin Cell Biol. 1993 Dec;5(6):1015–1022. doi: 10.1016/0955-0674(93)90086-6. [DOI] [PubMed] [Google Scholar]
  4. Brizuela B. J., Elfring L., Ballard J., Tamkun J. W., Kennison J. A. Genetic analysis of the brahma gene of Drosophila melanogaster and polytene chromosome subdivisions 72AB. Genetics. 1994 Jul;137(3):803–813. doi: 10.1093/genetics/137.3.803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chan S. K., Jaffe L., Capovilla M., Botas J., Mann R. S. The DNA binding specificity of Ultrabithorax is modulated by cooperative interactions with extradenticle, another homeoprotein. Cell. 1994 Aug 26;78(4):603–615. doi: 10.1016/0092-8674(94)90525-8. [DOI] [PubMed] [Google Scholar]
  6. Cheng N. N., Sinclair D. A., Campbell R. B., Brock H. W. Interactions of polyhomeotic with Polycomb group genes of Drosophila melanogaster. Genetics. 1994 Dec;138(4):1151–1162. doi: 10.1093/genetics/138.4.1151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Côté J., Quinn J., Workman J. L., Peterson C. L. Stimulation of GAL4 derivative binding to nucleosomal DNA by the yeast SWI/SNF complex. Science. 1994 Jul 1;265(5168):53–60. doi: 10.1126/science.8016655. [DOI] [PubMed] [Google Scholar]
  8. Duncan I. M. Polycomblike: a gene that appears to be required for the normal expression of the bithorax and antennapedia gene complexes of Drosophila melanogaster. Genetics. 1982 Sep;102(1):49–70. doi: 10.1093/genetics/102.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dura J. M., Brock H. W., Santamaria P. Polyhomeotic: a gene of Drosophila melanogaster required for correct expression of segmental identity. Mol Gen Genet. 1985;198(2):213–220. doi: 10.1007/BF00382998. [DOI] [PubMed] [Google Scholar]
  10. Farkas G., Gausz J., Galloni M., Reuter G., Gyurkovics H., Karch F. The Trithorax-like gene encodes the Drosophila GAGA factor. Nature. 1994 Oct 27;371(6500):806–808. doi: 10.1038/371806a0. [DOI] [PubMed] [Google Scholar]
  11. Felsenfeld A. L., Kennison J. A. Positional signaling by hedgehog in Drosophila imaginal disc development. Development. 1995 Jan;121(1):1–10. doi: 10.1242/dev.121.1.1. [DOI] [PubMed] [Google Scholar]
  12. Forbes A. J., Nakano Y., Taylor A. M., Ingham P. W. Genetic analysis of hedgehog signalling in the Drosophila embryo. Dev Suppl. 1993:115–124. [PubMed] [Google Scholar]
  13. Gertler F. B., Bennett R. L., Clark M. J., Hoffmann F. M. Drosophila abl tyrosine kinase in embryonic CNS axons: a role in axonogenesis is revealed through dosage-sensitive interactions with disabled. Cell. 1989 Jul 14;58(1):103–113. doi: 10.1016/0092-8674(89)90407-8. [DOI] [PubMed] [Google Scholar]
  14. Hayashi S., Scott M. P. What determines the specificity of action of Drosophila homeodomain proteins? Cell. 1990 Nov 30;63(5):883–894. doi: 10.1016/0092-8674(90)90492-w. [DOI] [PubMed] [Google Scholar]
  15. Heemskerk J., DiNardo S. Drosophila hedgehog acts as a morphogen in cellular patterning. Cell. 1994 Feb 11;76(3):449–460. doi: 10.1016/0092-8674(94)90110-4. [DOI] [PubMed] [Google Scholar]
  16. Ingham P. W. A gene that regulates the bithorax complex differentially in larval and adult cells of Drosophila. Cell. 1984 Jul;37(3):815–823. doi: 10.1016/0092-8674(84)90416-1. [DOI] [PubMed] [Google Scholar]
  17. Jones R. S., Gelbart W. M. The Drosophila Polycomb-group gene Enhancer of zeste contains a region with sequence similarity to trithorax. Mol Cell Biol. 1993 Oct;13(10):6357–6366. doi: 10.1128/mcb.13.10.6357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kaufman T. C., Seeger M. A., Olsen G. Molecular and genetic organization of the antennapedia gene complex of Drosophila melanogaster. Adv Genet. 1990;27:309–362. doi: 10.1016/s0065-2660(08)60029-2. [DOI] [PubMed] [Google Scholar]
  19. Kennison J. A., Tamkun J. W. Dosage-dependent modifiers of polycomb and antennapedia mutations in Drosophila. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8136–8140. doi: 10.1073/pnas.85.21.8136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kennison J. A. Transcriptional activation of Drosophila homeotic genes from distant regulatory elements. Trends Genet. 1993 Mar;9(3):75–79. doi: 10.1016/0168-9525(93)90227-9. [DOI] [PubMed] [Google Scholar]
  21. Kerrigan L. A., Croston G. E., Lira L. M., Kadonaga J. T. Sequence-specific transcriptional antirepression of the Drosophila Krüppel gene by the GAGA factor. J Biol Chem. 1991 Jan 5;266(1):574–582. [PubMed] [Google Scholar]
  22. Kuziora M. A., McGinnis W. Different transcripts of the Drosophila Abd-B gene correlate with distinct genetic sub-functions. EMBO J. 1988 Oct;7(10):3233–3244. doi: 10.1002/j.1460-2075.1988.tb03190.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Laughon A. DNA binding specificity of homeodomains. Biochemistry. 1991 Dec 3;30(48):11357–11367. doi: 10.1021/bi00112a001. [DOI] [PubMed] [Google Scholar]
  24. Lee J. J., von Kessler D. P., Parks S., Beachy P. A. Secretion and localized transcription suggest a role in positional signaling for products of the segmentation gene hedgehog. Cell. 1992 Oct 2;71(1):33–50. doi: 10.1016/0092-8674(92)90264-d. [DOI] [PubMed] [Google Scholar]
  25. Lewis E. B. A gene complex controlling segmentation in Drosophila. Nature. 1978 Dec 7;276(5688):565–570. doi: 10.1038/276565a0. [DOI] [PubMed] [Google Scholar]
  26. Lufkin T., Mark M., Hart C. P., Dollé P., LeMeur M., Chambon P. Homeotic transformation of the occipital bones of the skull by ectopic expression of a homeobox gene. Nature. 1992 Oct 29;359(6398):835–841. doi: 10.1038/359835a0. [DOI] [PubMed] [Google Scholar]
  27. Mann R. S. Engrailed-mediated repression of Ultrabithorax is necessary for the parasegment 6 identity in Drosophila. Development. 1994 Nov;120(11):3205–3212. doi: 10.1242/dev.120.11.3205. [DOI] [PubMed] [Google Scholar]
  28. McGinnis W., Jack T., Chadwick R., Regulski M., Bergson C., McGinnis N., Kuziora M. A. Establishment and maintenance of position-specific expression of the Drosophila homeotic selector gene Deformed. Adv Genet. 1990;27:363–402. doi: 10.1016/s0065-2660(08)60030-9. [DOI] [PubMed] [Google Scholar]
  29. McGinnis W., Krumlauf R. Homeobox genes and axial patterning. Cell. 1992 Jan 24;68(2):283–302. doi: 10.1016/0092-8674(92)90471-n. [DOI] [PubMed] [Google Scholar]
  30. Merrill V. K., Turner F. R., Kaufman T. C. A genetic and developmental analysis of mutations in the Deformed locus in Drosophila melanogaster. Dev Biol. 1987 Aug;122(2):379–395. doi: 10.1016/0012-1606(87)90303-4. [DOI] [PubMed] [Google Scholar]
  31. Mohler J., Mahaffey J. W., Deutsch E., Vani K. Control of Drosophila head segment identity by the bZIP homeotic gene cnc. Development. 1995 Jan;121(1):237–247. doi: 10.1242/dev.121.1.237. [DOI] [PubMed] [Google Scholar]
  32. Mohler J. Requirements for hedgehog, a segmental polarity gene, in patterning larval and adult cuticle of Drosophila. Genetics. 1988 Dec;120(4):1061–1072. doi: 10.1093/genetics/120.4.1061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Mohler J., Vani K., Leung S., Epstein A. Segmentally restricted, cephalic expression of a leucine zipper gene during Drosophila embryogenesis. Mech Dev. 1991 Mar;34(1):3–9. doi: 10.1016/0925-4773(91)90086-l. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. Paro R., Hogness D. S. The Polycomb protein shares a homologous domain with a heterochromatin-associated protein of Drosophila. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):263–267. doi: 10.1073/pnas.88.1.263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Paro R. Imprinting a determined state into the chromatin of Drosophila. Trends Genet. 1990 Dec;6(12):416–421. doi: 10.1016/0168-9525(90)90303-n. [DOI] [PubMed] [Google Scholar]
  37. Pattatucci A. M., Kaufman T. C. The homeotic gene Sex combs reduced of Drosophila melanogaster is differentially regulated in the embryonic and imaginal stages of development. Genetics. 1991 Oct;129(2):443–461. doi: 10.1093/genetics/129.2.443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Peifer M., Wieschaus E. Mutations in the Drosophila gene extradenticle affect the way specific homeo domain proteins regulate segmental identity. Genes Dev. 1990 Jul;4(7):1209–1223. doi: 10.1101/gad.4.7.1209. [DOI] [PubMed] [Google Scholar]
  39. Peterson C. L., Herskowitz I. Characterization of the yeast SWI1, SWI2, and SWI3 genes, which encode a global activator of transcription. Cell. 1992 Feb 7;68(3):573–583. doi: 10.1016/0092-8674(92)90192-f. [DOI] [PubMed] [Google Scholar]
  40. Phillips M. D., Shearn A. Mutations in polycombeotic, a Drosophila polycomb-group gene, cause a wide range of maternal and zygotic phenotypes. Genetics. 1990 May;125(1):91–101. doi: 10.1093/genetics/125.1.91. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Raftery L. A., Twombly V., Wharton K., Gelbart W. M. Genetic screens to identify elements of the decapentaplegic signaling pathway in Drosophila. Genetics. 1995 Jan;139(1):241–254. doi: 10.1093/genetics/139.1.241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Ramírez-Solis R., Zheng H., Whiting J., Krumlauf R., Bradley A. Hoxb-4 (Hox-2.6) mutant mice show homeotic transformation of a cervical vertebra and defects in the closure of the sternal rudiments. Cell. 1993 Apr 23;73(2):279–294. doi: 10.1016/0092-8674(93)90229-j. [DOI] [PubMed] [Google Scholar]
  43. Rastelli L., Chan C. S., Pirrotta V. Related chromosome binding sites for zeste, suppressors of zeste and Polycomb group proteins in Drosophila and their dependence on Enhancer of zeste function. EMBO J. 1993 Apr;12(4):1513–1522. doi: 10.1002/j.1460-2075.1993.tb05795.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Rauskolb C., Peifer M., Wieschaus E. extradenticle, a regulator of homeotic gene activity, is a homolog of the homeobox-containing human proto-oncogene pbx1. Cell. 1993 Sep 24;74(6):1101–1112. doi: 10.1016/0092-8674(93)90731-5. [DOI] [PubMed] [Google Scholar]
  45. Regulski M., Dessain S., McGinnis N., McGinnis W. High-affinity binding sites for the Deformed protein are required for the function of an autoregulatory enhancer of the Deformed gene. Genes Dev. 1991 Feb;5(2):278–286. doi: 10.1101/gad.5.2.278. [DOI] [PubMed] [Google Scholar]
  46. Sato T., Russell M. A., Denell R. E. Homoeosis in Drosophila: a new enhancer of polycomb and related homoeotic mutations. Genetics. 1983 Oct;105(2):357–370. doi: 10.1093/genetics/105.2.357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Sedkov Y., Tillib S., Mizrokhi L., Mazo A. The bithorax complex is regulated by trithorax earlier during Drosophila embryogenesis than is the Antennapedia complex, correlating with a bithorax-like expression pattern of distinct early trithorax transcripts. Development. 1994 Jul;120(7):1907–1917. doi: 10.1242/dev.120.7.1907. [DOI] [PubMed] [Google Scholar]
  48. Siegfried E., Wilder E. L., Perrimon N. Components of wingless signalling in Drosophila. Nature. 1994 Jan 6;367(6458):76–80. doi: 10.1038/367076a0. [DOI] [PubMed] [Google Scholar]
  49. Simon J., Chiang A., Bender W. Ten different Polycomb group genes are required for spatial control of the abdA and AbdB homeotic products. Development. 1992 Feb;114(2):493–505. doi: 10.1242/dev.114.2.493. [DOI] [PubMed] [Google Scholar]
  50. Simon M. A., Bowtell D. D., Dodson G. S., Laverty T. R., Rubin G. M. Ras1 and a putative guanine nucleotide exchange factor perform crucial steps in signaling by the sevenless protein tyrosine kinase. Cell. 1991 Nov 15;67(4):701–716. doi: 10.1016/0092-8674(91)90065-7. [DOI] [PubMed] [Google Scholar]
  51. Struhl G. A gene product required for correct initiation of segmental determination in Drosophila. Nature. 1981 Sep 3;293(5827):36–41. doi: 10.1038/293036a0. [DOI] [PubMed] [Google Scholar]
  52. Struhl G. Role of the esc+ gene product in ensuring the selective expression of segment-specific homeotic genes in Drosophila. J Embryol Exp Morphol. 1983 Aug;76:297–331. [PubMed] [Google Scholar]
  53. Tamkun J. W., Deuring R., Scott M. P., Kissinger M., Pattatucci A. M., Kaufman T. C., Kennison J. A. brahma: a regulator of Drosophila homeotic genes structurally related to the yeast transcriptional activator SNF2/SWI2. Cell. 1992 Feb 7;68(3):561–572. doi: 10.1016/0092-8674(92)90191-e. [DOI] [PubMed] [Google Scholar]
  54. Tripoulas N. A., Hersperger E., La Jeunesse D., Shearn A. Molecular genetic analysis of the Drosophila melanogaster gene absent, small or homeotic discs1 (ash1). Genetics. 1994 Aug;137(4):1027–1038. doi: 10.1093/genetics/137.4.1027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Tsukiyama T., Becker P. B., Wu C. ATP-dependent nucleosome disruption at a heat-shock promoter mediated by binding of GAGA transcription factor. Nature. 1994 Feb 10;367(6463):525–532. doi: 10.1038/367525a0. [DOI] [PubMed] [Google Scholar]
  56. Wedeen C., Harding K., Levine M. Spatial regulation of Antennapedia and bithorax gene expression by the Polycomb locus in Drosophila. Cell. 1986 Mar 14;44(5):739–748. doi: 10.1016/0092-8674(86)90840-8. [DOI] [PubMed] [Google Scholar]
  57. Zeng C., Pinsonneault J., Gellon G., McGinnis N., McGinnis W. Deformed protein binding sites and cofactor binding sites are required for the function of a small segment-specific regulatory element in Drosophila embryos. EMBO J. 1994 May 15;13(10):2362–2377. doi: 10.1002/j.1460-2075.1994.tb06520.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. van Dijk M. A., Murre C. extradenticle raises the DNA binding specificity of homeotic selector gene products. Cell. 1994 Aug 26;78(4):617–624. doi: 10.1016/0092-8674(94)90526-6. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES