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JOURNAL ARTICLES
Genetic evidence that heparin-like glycosaminoglycans are involved in wingless signaling
R.C. Binari, B.E. Staveley, W.A. Johnson, R. Godavarti, R. Sasisekharan, A.S. Manoukian
Development 1997 124: 2623-2632;

Summary

We have identified the Drosophila UDP-glucose dehydrogenase gene as being involved in wingless signaling. Mutations in this gene, called kiwi, generate a phenotype identical to that of wingless. UDP-glucose dehydrogenase is required for the biosynthesis of UDP-glucuronate, which in turn is utilized in the biosynthesis of glycosaminoglycans. By rescuing the kiwi phenotype with both UDP-glucuronate and the glycosaminoglycan heparan sulfate, we show that kiwi function in the embryo is crucial for the production of heparan sulfate in the extracellular matrix. Further, injection of heparin degrading enzyme, heparinase (and not chondroitin, dermatan or hyaluronic acid degrading enzyme) into wild-type embryos leads to the degradation of heparin-like glycosaminoglycans and a ‘wingless-like’ cuticular phenotype. Our study thus provides the first genetic evidence for the involvement of heparin-like glycosaminoglycans in signal transduction.

REFERENCES

    1. Altschul S. F.,
    2. Gish W.,
    3. Miller W.,
    4. Myers E. W.,
    5. Lipman D. J.
    (1990) Basic Local alignment search tool. J. Mol. Biol 215, 403–410
    OpenUrlCrossRefPubMedWeb of Science
    1. Anderson M. G.,
    2. Perkins G. L.,
    3. Chittick P.,
    4. Shrigley R. J.,
    5. Johnson W. A.
    (1995) drifter, a Drosophila POU-domain transcription factor, is required for correct differentiation and migration of tracheal cells and midline glia. Genes Dev 9, 123–137
    OpenUrlAbstract/FREE Full Text
    1. Bhanot P.,
    2. Brink M.,
    3. Samos C. H.,
    4. Hsieh J.-C.,
    5. Wang Y.,
    6. Macke J. P.,
    7. Andrew D.,
    8. Nathans J.,
    9. Nusse R.
    (1996) A new member of the frizzled family from Drosophila functions as a Wingless receptor. Nature 382, 225–230
    OpenUrlCrossRefPubMedWeb of Science
    1. Birnstiel M. L.,
    2. Busslinger M.,
    3. Strub K.
    (1985) Transcription termination and 3processing: The end is in site!. Cell 41, 349–359
    OpenUrlCrossRefPubMedWeb of Science
    1. Blackman R. K.,
    2. Grimaila R.,
    3. Koehler M.,
    4. Gelbart W. M.
    (1987) Mobilization of hobo elements residing within the Decapentaplegic gene complex: Suggestion of a new hybrid dysgenesis system in Drosophila melanogaster. Cell 49, 497–505
    OpenUrlCrossRefPubMedWeb of Science
    1. Bradley R. S.,
    2. Brown A. M.
    (1990) The proto-oncogene int-1 encodes a secreted protein associated with the extracellular matrix. EMBO J 9, 1569–1575
    OpenUrlPubMedWeb of Science
    1. Brand A. H.,
    2. Perrimon N.
    (1993) Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118, 401–415
    OpenUrlAbstract
    1. Brown N. H.,
    2. Kafatos F. C.
    (1988) Functional cDNA libraries from Drosophila embryos. J. Mol. Biol 203, 425–437
    OpenUrlCrossRefPubMedWeb of Science
    1. Burrus L. W.,
    2. McMahon A. P.
    (1995) Biochemical analysis of murine Wnt proteins reveals both shared and distinct properties. Exp. Cell Res 220, 363–373
    OpenUrlCrossRefPubMedWeb of Science
    1. Cavener D. R.
    (1987) Comparison of the consensus sequence flanking translational start sites in Drosophila and vertebrates. Nucl. Acids Res 4, 1353–1361
    OpenUrl
    1. Chou T.-B.,
    2. Perrimon N.
    (1996) The autosomal FLP-DFS technique for generating germline mosaics in Drosophilamelanogaster. Genetics 144, 1673–1679
    OpenUrlAbstract/FREE Full Text
    1. Couso J. P.,
    2. Bishop S. A.,
    3. Martinez-Arias A.
    (1994) The wingless signaling pathway and the patterning of the wing margin in Drosophila. Development 120, 621–636
    OpenUrlAbstract
    1. DiNardo S.,
    2. Sher E.,
    3. Heemskerk-Jongens J.,
    4. Kassis J.A.,
    5. O'Farrell P.H.
    (1988) Two-tiered regulation of spatially patterned engrailed gene expression during Drosophila embryogenesis. Nature 332, 604–609
    OpenUrlCrossRefPubMed
    1. Dougherty B. A.,
    2. van de Rijn I.
    (1993) Molecular characterization of hasB from an operon required for hyaluronic acid synthesis in group A Streptococci. J. Biol. Chem 268, 7118–7124
    OpenUrlAbstract/FREE Full Text
    1. Ernst S.,
    2. Langer R.,
    3. Cooney C. L.,
    4. Sasisekharan R.
    (1995) Enzymatic degradation of glycosaminoglycans. Critical Rev. Biochem. Mol. Biol 30, 387–444
    OpenUrlCrossRefPubMedWeb of Science
    1. Ernst S.,
    2. Venkataraman G.,
    3. Winkler S.,
    4. Godavarti R.,
    5. Langer R.,
    6. Cooney C. L.,
    7. Sasisekharan R.
    (1996) Expression in Escherichia coli, purification and characterization of heparinase I from Flavobacterium heparinum. Biochem. J 315, 589–597
    1. Feinberg A. P.,
    2. Vogelstein B.
    (1983) A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal. Biochem 132, 6–13
    OpenUrlCrossRefPubMedWeb of Science
    1. Feingold D. S.,
    2. Franzen J. S.
    (1981) Pyridine nucleotide-linked four-electron transfer dehydrogenase. Trends Biochem. Sci 6, 103–105
    1. Hempel J.,
    2. Perozich J.,
    3. Romovacek H.,
    4. Hinich A.,
    5. Kuo I.,
    6. Feingold D. S.
    (1994) UDP-glucose dehydrogenase from bovine liver: primary structure and relationship to other dehydrogenases. Protein Sci 3, 1074–1080
    OpenUrlCrossRefPubMedWeb of Science
    1. Jackson R. L.,
    2. Busch S. J.,
    3. Cardin A. D.
    (1991) Glycosaminoglycans: molecular properties, protein interactions, and role in physiological processes. Physiol. Rev 71, 481–539
    OpenUrlFREE Full Text
    1. Jue S. F.,
    2. Bradley R. S.,
    3. Rudnicki J. A.,
    4. Varmus H. E.,
    5. Brown A. M. C.
    (1992) The mouse Wnt-1 gene can act via a paracrine mechanism in transformation of mammary epithelial cells. Mol. Cell. Biol 12, 321–328
    OpenUrlAbstract/FREE Full Text
    1. Kjellan L.,
    2. Lindahl U.
    (1991) Proteoglycans: structures and interactions. Annu. Rev. Biochem 60, 443–475
    OpenUrlCrossRefPubMedWeb of Science
    1. Klagsbrun M.,
    2. Baird A.
    (1991) A dual receptor system is required for basic fibroblast growth factor activity. Cell 67, 229–231
    OpenUrlCrossRefPubMedWeb of Science
    1. Klingensmith J.,
    2. Nusse R.
    (1994) Signaling by wingless in Drosophila. Dev. Biol 166, 396–414
    OpenUrlCrossRefPubMedWeb of Science
    1. Lawrence P. A.,
    2. Struhl G.
    (1996) Morphogens, compartments and pattern: Lessons from Drosophila?. Cell 85, 951–961
    OpenUrlCrossRefPubMedWeb of Science
    1. Manoukian A. S.,
    2. Krause H. M.
    (1992) Concentration-dependent regulatory activities of the even-skipped protein in Drosophila embryos. Genes Dev 6, 1740–1751
    OpenUrlAbstract/FREE Full Text
    1. Manoukian A. S.,
    2. Yoffe K. B.,
    3. Wilder E. L.,
    4. Perrimon N.
    (1995) The porcupine gene is required for wingless autoregulation in Drosophila. Development 121, 4037–4044
    OpenUrlAbstract
    1. Martinez-Arias A.,
    2. Baker N.,
    3. Ingham P. W.
    (1988) Role of segment polarity genes in the definition and maintenance of cell states in the Drosophila embryo. Development 103, 157–170
    OpenUrlAbstract
    1. McCrea P. D.,
    2. Turck C. W.,
    3. Gumbiner B.
    (1991) A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin. Science 254, 1359–1361
    OpenUrlAbstract/FREE Full Text
    1. McMahon A. P.
    (1992) The Wnt family of developmental regulators. Trends Genet 8, 236–242
    1. McMahon A. P.,
    2. Bradley A.
    (1990) The Wnt-1 (int-1) proto-oncogene is required for development of a large region of the mouse brain. Cell 62, 1073–1085
    OpenUrlCrossRefPubMedWeb of Science
    1. Noordermeer J.,
    2. Johnston P.,
    3. Rijsewijk F.,
    4. Nusse R.,
    5. Lawrence P. A.
    (1992) The consequences of ubiquitous expression of the wingless gene in the Drosophila embryo. Development 116, 711–719
    OpenUrlAbstract
    1. Nusse R.,
    2. Varmus H. E.
    (1992) Wnt genes. Cell 69, 1073–1087
    OpenUrlCrossRefPubMedWeb of Science
    1. Ornitz D. M.,
    2. Yayon A.,
    3. Flanagan J. G.,
    4. Svahn C. M.,
    5. Levi E.,
    6. Leder P.
    (1992) Heparin is required for cell-free binding of basic fibroblast growth factor to a soluble receptor and for mitogenesis in whole cells. Mol. Cell. Biol 12, 240–247
    OpenUrlAbstract/FREE Full Text
    1. Papkoff J.,
    2. Schryver B.
    (1990) Secreted int-1 protein is associated with the cell surface. Mol. Cell. Biol 10, 2723–2730
    OpenUrlAbstract/FREE Full Text
    1. Perrimon N.,
    2. Engstrom L.,
    3. Mahowald A. P.
    (1989). Zygotic lethals with specific maternal effect phenotypes in Drosophila melanogaster. I. Loci on the X chromosome. Genetics 121, 333–352
    OpenUrlAbstract/FREE Full Text
    1. Reichsman F.,
    2. Smith L.,
    3. Cumberledge S.
    (1996) Glycosaminoglycans can modulate extracellular localization of the wingless protein and promote signal transduction. J. Cell Biol 135, 819–827
    OpenUrlAbstract/FREE Full Text
    1. Robertson H. M.,
    2. Preston C. R.,
    3. Phillis R. W.,
    4. Johnson-Schlitz D. M.,
    5. Benz W. K.,
    6. Engels W. R.
    (1988) A stable source of P element transposase in Drosophilamelanogaster. Genetics 118, 461–470
    OpenUrlAbstract/FREE Full Text
    1. Schlessinger J.,
    2. Lax I.,
    3. Lemmon M.
    (1995) Regulation of growth factor activation by proteoglycans: what is the role of the low affinity receptors?. Cell 83, 357–360
    OpenUrlCrossRefPubMedWeb of Science
    1. Schryver B.,
    2. Hinck L.,
    3. Papkoff J.
    (1996) Properties of Wnt-1 protein that enable cell surface association. Oncogene 13, 333–342
    OpenUrlPubMed
    1. Siegfried E.,
    2. Chou T. B.,
    3. Perrimon N.
    (1992) wingless signaling acts through zeste-white 3, the Drosophila homologue of glycogen synthase kinase-3, to regulate engrailed and establish cell fate. Cell 71, 1167–1179
    OpenUrlCrossRefPubMedWeb of Science
    1. Spradling A. C.,
    2. Stern D. M.,
    3. Kiss I.,
    4. Roote J.,
    5. Laverty T.,
    6. Rubin G. M.
    (1995) Gene disruptions using P transposable elements: An integral component of the Drosophila genome project. Proc. Natl. Acad. Sci.USA 92, 10824–10830
    OpenUrlAbstract/FREE Full Text
    1. Thomas K. R.,
    2. Capecchi M. R.
    (1990) Targeted disruption of the murine int-1 proto-oncogene resulting in severe abnormalities in midbrain and cerebellar development. Nature 346, 847–850
    OpenUrlCrossRefPubMedWeb of Science
    1. van den Heuvel M.,
    2. Ingham P. W.
    (1996) smoothened encodes a receptor-like serpentine protein required for hedgehog signalling. Nature 382, 547–551
    OpenUrlCrossRefPubMedWeb of Science
    1. Zecca M.,
    2. Basler K.,
    3. Struhl G.
    (1996) Direct and long-range action of a Wingless morphogen gradient. Cell 87, 833–844
    OpenUrlCrossRefPubMedWeb of Science
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JOURNAL ARTICLES
Genetic evidence that heparin-like glycosaminoglycans are involved in wingless signaling
R.C. Binari, B.E. Staveley, W.A. Johnson, R. Godavarti, R. Sasisekharan, A.S. Manoukian
Development 1997 124: 2623-2632;
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