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. 1994 Aug 1;13(15):3561–3569. doi: 10.1002/j.1460-2075.1994.tb06663.x

Coordinate regulation of downstream genes by extradenticle and the homeotic selector proteins.

C Rauskolb 1, E Wieschaus 1
PMCID: PMC395260  PMID: 7914871

Abstract

Mutations in the Drosophila gene extradenticle (exd), a homologue of the human proto-oncogene pbx1, cause homeotic transformations by altering the morphological consequences of homeotic selector gene activity. exd has been proposed to act by contributing to the specificity of selector homeodomain proteins for their downstream targets. Here we show that exd is indeed required for the appropriate regulation of at least some of these target genes. Expression patterns of wingless, teashirt and decapentaplegic (dpp) are altered in the embryonic midgut of embryos lacking exd, while the expression of their respective regulators (abd-A, Antp and Ubx) remains normal. Co-regulation of dpp by exd and Ubx was investigated in greater detail by examining the expression of reporter constructs in exd embryos. These experiments not only define dpp regulatory regions responsive to exd, but also distinguish two functions of exd in the regulation of dpp. exd acts with Ubx to activate dpp expression in parasegment 7 (PS7), via a minimal visceral mesoderm enhancer, and exd represses dpp expression anterior to PS7. We show that even when Ubx is ubiquitously expressed at high levels in exd embryos, Ubx is incapable of activating dpp enhancer expression. Thus, exd is an indispensable component in target gene regulation by the homeotic selector proteins.

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Selected References

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

  1. Bienz M., Saari G., Tremml G., Müller J., Züst B., Lawrence P. A. Differential regulation of Ultrabithorax in two germ layers of Drosophila. Cell. 1988 May 20;53(4):567–576. doi: 10.1016/0092-8674(88)90573-9. [DOI] [PubMed] [Google Scholar]
  2. Bienz M., Tremml G. Domain of Ultrabithorax expression in Drosophila visceral mesoderm from autoregulation and exclusion. Nature. 1988 Jun 9;333(6173):576–578. doi: 10.1038/333576a0. [DOI] [PubMed] [Google Scholar]
  3. Bürglin T. R., Ruvkun G. New motif in PBX genes. Nat Genet. 1992 Aug;1(5):319–320. doi: 10.1038/ng0892-319. [DOI] [PubMed] [Google Scholar]
  4. Capovilla M., Brandt M., Botas J. Direct regulation of decapentaplegic by Ultrabithorax and its role in Drosophila midgut morphogenesis. Cell. 1994 Feb 11;76(3):461–475. doi: 10.1016/0092-8674(94)90111-2. [DOI] [PubMed] [Google Scholar]
  5. Desplan C., Theis J., O'Farrell P. H. The sequence specificity of homeodomain-DNA interaction. Cell. 1988 Sep 23;54(7):1081–1090. doi: 10.1016/0092-8674(88)90123-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fasano L., Röder L., Coré N., Alexandre E., Vola C., Jacq B., Kerridge S. The gene teashirt is required for the development of Drosophila embryonic trunk segments and encodes a protein with widely spaced zinc finger motifs. Cell. 1991 Jan 11;64(1):63–79. doi: 10.1016/0092-8674(91)90209-h. [DOI] [PubMed] [Google Scholar]
  7. Flegel W. A., Singson A. W., Margolis J. S., Bang A. G., Posakony J. W., Murre C. Dpbx, a new homeobox gene closely related to the human proto-oncogene pbx1 molecular structure and developmental expression. Mech Dev. 1993 May;41(2-3):155–161. doi: 10.1016/0925-4773(93)90045-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Glicksman M. A., Brower D. L. Expression of the Sex combs reduced protein in Drosophila larvae. Dev Biol. 1988 May;127(1):113–118. doi: 10.1016/0012-1606(88)90193-5. [DOI] [PubMed] [Google Scholar]
  9. Goutte C., Johnson A. D. Yeast a1 and alpha 2 homeodomain proteins form a DNA-binding activity with properties distinct from those of either protein. J Mol Biol. 1993 Oct 5;233(3):359–371. doi: 10.1006/jmbi.1993.1517. [DOI] [PubMed] [Google Scholar]
  10. Grueneberg D. A., Natesan S., Alexandre C., Gilman M. Z. Human and Drosophila homeodomain proteins that enhance the DNA-binding activity of serum response factor. Science. 1992 Aug 21;257(5073):1089–1095. doi: 10.1126/science.257.5073.1089. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Hoey T., Levine M. Divergent homeo box proteins recognize similar DNA sequences in Drosophila. Nature. 1988 Apr 28;332(6167):858–861. doi: 10.1038/332858a0. [DOI] [PubMed] [Google Scholar]
  13. Hursh D. A., Padgett R. W., Gelbart W. M. Cross regulation of decapentaplegic and Ultrabithorax transcription in the embryonic visceral mesoderm of Drosophila. Development. 1993 Apr;117(4):1211–1222. doi: 10.1242/dev.117.4.1211. [DOI] [PubMed] [Google Scholar]
  14. Immerglück K., Lawrence P. A., Bienz M. Induction across germ layers in Drosophila mediated by a genetic cascade. Cell. 1990 Jul 27;62(2):261–268. doi: 10.1016/0092-8674(90)90364-k. [DOI] [PubMed] [Google Scholar]
  15. Irvine K. D., Helfand S. L., Hogness D. S. The large upstream control region of the Drosophila homeotic gene Ultrabithorax. Development. 1991 Feb;111(2):407–424. doi: 10.1242/dev.111.2.407. [DOI] [PubMed] [Google Scholar]
  16. Johnson F. B., Krasnow M. A. Stimulation of transcription by an Ultrabithorax protein in vitro. Genes Dev. 1990 Jun;4(6):1044–1052. doi: 10.1101/gad.4.6.1044. [DOI] [PubMed] [Google Scholar]
  17. Kellerman K. A., Mattson D. M., Duncan I. Mutations affecting the stability of the fushi tarazu protein of Drosophila. Genes Dev. 1990 Nov;4(11):1936–1950. doi: 10.1101/gad.4.11.1936. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Krasnow M. A., Saffman E. E., Kornfeld K., Hogness D. S. Transcriptional activation and repression by Ultrabithorax proteins in cultured Drosophila cells. Cell. 1989 Jun 16;57(6):1031–1043. doi: 10.1016/0092-8674(89)90341-3. [DOI] [PubMed] [Google Scholar]
  20. Lai J. S., Cleary M. A., Herr W. A single amino acid exchange transfers VP16-induced positive control from the Oct-1 to the Oct-2 homeo domain. Genes Dev. 1992 Nov;6(11):2058–2065. doi: 10.1101/gad.6.11.2058. [DOI] [PubMed] [Google Scholar]
  21. Levine M., Hoey T. Homeobox proteins as sequence-specific transcription factors. Cell. 1988 Nov 18;55(4):537–540. doi: 10.1016/0092-8674(88)90209-7. [DOI] [PubMed] [Google Scholar]
  22. Mann R. S., Hogness D. S. Functional dissection of Ultrabithorax proteins in D. melanogaster. Cell. 1990 Feb 23;60(4):597–610. doi: 10.1016/0092-8674(90)90663-y. [DOI] [PubMed] [Google Scholar]
  23. Manoukian A. S., Krause H. M. Concentration-dependent activities of the even-skipped protein in Drosophila embryos. Genes Dev. 1992 Sep;6(9):1740–1751. doi: 10.1101/gad.6.9.1740. [DOI] [PubMed] [Google Scholar]
  24. Masucci J. D., Hoffmann F. M. Identification of two regions from the Drosophila decapentaplegic gene required for embryonic midgut development and larval viability. Dev Biol. 1993 Sep;159(1):276–287. doi: 10.1006/dbio.1993.1240. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Panganiban G. E., Reuter R., Scott M. P., Hoffmann F. M. A Drosophila growth factor homolog, decapentaplegic, regulates homeotic gene expression within and across germ layers during midgut morphogenesis. Development. 1990 Dec;110(4):1041–1050. doi: 10.1242/dev.110.4.1041. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Percival-Smith A., Müller M., Affolter M., Gehring W. J. The interaction with DNA of wild-type and mutant fushi tarazu homeodomains. EMBO J. 1990 Dec;9(12):3967–3974. doi: 10.1002/j.1460-2075.1990.tb07617.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Pomerantz J. L., Kristie T. M., Sharp P. A. Recognition of the surface of a homeo domain protein. Genes Dev. 1992 Nov;6(11):2047–2057. doi: 10.1101/gad.6.11.2047. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Reuter R., Panganiban G. E., Hoffmann F. M., Scott M. P. Homeotic genes regulate the spatial expression of putative growth factors in the visceral mesoderm of Drosophila embryos. Development. 1990 Dec;110(4):1031–1040. doi: 10.1242/dev.110.4.1031. [DOI] [PubMed] [Google Scholar]
  32. Reuter R., Scott M. P. Expression and function of the homoeotic genes Antennapedia and Sex combs reduced in the embryonic midgut of Drosophila. Development. 1990 Jun;109(2):289–303. doi: 10.1242/dev.109.2.289. [DOI] [PubMed] [Google Scholar]
  33. Scott M. P., Tamkun J. W., Hartzell G. W., 3rd The structure and function of the homeodomain. Biochim Biophys Acta. 1989 Jul 28;989(1):25–48. doi: 10.1016/0304-419x(89)90033-4. [DOI] [PubMed] [Google Scholar]
  34. Smith D. L., Johnson A. D. A molecular mechanism for combinatorial control in yeast: MCM1 protein sets the spacing and orientation of the homeodomains of an alpha 2 dimer. Cell. 1992 Jan 10;68(1):133–142. doi: 10.1016/0092-8674(92)90212-u. [DOI] [PubMed] [Google Scholar]
  35. St Johnston R. D., Hoffmann F. M., Blackman R. K., Segal D., Grimaila R., Padgett R. W., Irick H. A., Gelbart W. M. Molecular organization of the decapentaplegic gene in Drosophila melanogaster. Genes Dev. 1990 Jul;4(7):1114–1127. doi: 10.1101/gad.4.7.1114. [DOI] [PubMed] [Google Scholar]
  36. Thali M., Müller M. M., DeLorenzi M., Matthias P., Bienz M. Drosophila homoeotic genes encode transcriptional activators similar to mammalian OTF-2. Nature. 1988 Dec 8;336(6199):598–601. doi: 10.1038/336598a0. [DOI] [PubMed] [Google Scholar]
  37. Tremml G., Bienz M. Homeotic gene expression in the visceral mesoderm of Drosophila embryos. EMBO J. 1989 Sep;8(9):2677–2685. doi: 10.1002/j.1460-2075.1989.tb08408.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. White R. A., Wilcox M. Protein products of the bithorax complex in Drosophila. Cell. 1984 Nov;39(1):163–171. doi: 10.1016/0092-8674(84)90202-2. [DOI] [PubMed] [Google Scholar]
  39. Wilson D., Sheng G., Lecuit T., Dostatni N., Desplan C. Cooperative dimerization of paired class homeo domains on DNA. Genes Dev. 1993 Nov;7(11):2120–2134. doi: 10.1101/gad.7.11.2120. [DOI] [PubMed] [Google Scholar]
  40. Winslow G. M., Hayashi S., Krasnow M., Hogness D. S., Scott M. P. Transcriptional activation by the Antennapedia and fushi tarazu proteins in cultured Drosophila cells. Cell. 1989 Jun 16;57(6):1017–1030. doi: 10.1016/0092-8674(89)90340-1. [DOI] [PubMed] [Google Scholar]
  41. Xue D., Tu Y., Chalfie M. Cooperative interactions between the Caenorhabditis elegans homeoproteins UNC-86 and MEC-3. Science. 1993 Sep 3;261(5126):1324–1328. doi: 10.1126/science.8103239. [DOI] [PubMed] [Google Scholar]
  42. 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]

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