Advertisement
JOURNAL ARTICLES
Functional analysis of Wingless reveals a link between intercellular ligand transport and dorsal-cell-specific signaling
H.A. Dierick, A. Bejsovec
Development 1998 125: 4729-4738;

Summary

The Drosophila segment polarity gene wingless (wg) is essential for cell fate decisions in the developing embryonic epidermis. Wg protein is produced in one row of cells near the posterior of every segment and is secreted and distributed throughout the segment to generate wild-type pattern elements. Ventrally, epidermal cells secrete a diverse array of anterior denticle types and a posterior expanse of naked cuticle; dorsally, a stereotyped pattern of fine hairs is secreted. We describe three new wg alleles that promote naked cuticle cell fate but show reduced denticle diversity and dorsal patterning. These mutations cause single amino acid substitutions in a cluster of residues that are highly conserved throughout the Wnt family. By manipulating expression of transgenic proteins, we demonstrate that all three mutant molecules retain the intrinsic capacity to signal ventrally but fail to be distributed across the segment. Thus, movement of Wg protein through the epidermal epithelium is essential for proper ventral denticle specification and this planar movement is distinct from the apical-basal transcytosis previously described in polarized epithelia. Furthermore, ectopic overexpression of the mutant proteins fails to rescue dorsal pattern elements. Thus we have identified a region of Wingless that is required for both the transcytotic process and signal transduction in dorsal cell populations, revealing an unexpected link between these two aspects of Wg function.

REFERENCES

    1. Baker N. E.
    (1987) Molecular cloning of sequences from wingless, a segment polarity gene in Drosophila: the spatial distribution of a transcript in embryos. EMBO J 6, 1765–1773
    OpenUrlPubMedWeb of Science
    1. Baker N. E.
    (1988) Embryonic and imaginal requirements for wingless, a segment polarity gene in Drosophila. Dev. Biol 125, 96–108
    OpenUrlCrossRefPubMedWeb of Science
    1. Bejsovec A.,
    2. Martinez-Arias A.
    (1991) Roles of wingless in patterning the larval epidermis of Drosophila. Development 113, 471–485
    OpenUrlAbstract
    1. Bejsovec A.,
    2. Wieschaus E.
    (1993) Segment polarity gene interactions modulate epidermal patterning in Drosophila embryos. Development 119, 501–517
    OpenUrlAbstract
    1. Bejsovec A.,
    2. Wieschaus E.
    (1995) Signaling activities of the Drosophila wingless gene are separately mutable and appear to be transduced at the cell surface. Genetics 139, 309–320
    OpenUrlAbstract/FREE Full Text
    1. Binari R. C.,
    2. Staveley B. E.,
    3. Johnson W. A.,
    4. Godavarti R.,
    5. Sasisekharan R.,
    6. Manoukian A. S.
    (1997) Genetic evidence that heparin-like glycosaminoglycans are involved in wingless signaling. Development 124, 2623–2632
    OpenUrlAbstract
    1. Bradley R. S.,
    2. Brown A. M. C.
    (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 meansof altering cell fates and generating dominant phenotypes. Development 118, 401–415
    OpenUrlAbstract
    1. Brunner E.,
    2. Peter O.,
    3. Schweizer L.,
    4. Basler K.
    (1997) pangolin encodes a Lef-1 homolog that acts downstream of Armadillo to transduce the Wingless signal. Nature 385, 829–833
    OpenUrlCrossRefPubMedWeb of Science
    1. Buenzow D.,
    2. Holmgren R.
    (1995) Expression of the Drosophila gooseberry locus defines a subset of neuroblast lineages in the central nervous system. Dev. Biol 170, 338–349
    OpenUrlCrossRefPubMedWeb of Science
    1. Cadigan K. M.,
    2. Fish M. P.,
    3. Rulifson E. J.,
    4. Nusse R.
    (1998) Wingless repression of Drosophila frizzled 2 expression shapes the Wingless morphogen gradient in the wing. Cell 93, 767–777
    OpenUrlCrossRefPubMedWeb of Science
    1. Cavallo R. A.,
    2. Cox R. T.,
    3. Moline M. M.,
    4. Roose J.,
    5. Polevoy G. A.,
    6. Clevers H.,
    7. Peifer M.,
    8. Bejsovec A.
    (1998) Drosophila TCF and Groucho interact to repress Wingless signaling activity. Nature 395, 604–608
    OpenUrlCrossRefPubMedWeb of Science
    1. Chen Y.,
    2. Struhl G.
    (1996) Dual roles for patched in sequestering and transducing hedgehog. Cell 87, 553–563
    OpenUrlCrossRefPubMedWeb of Science
    1. DiNardo S.,
    2. Sher E.,
    3. Heemskerk-Jongens J.,
    4. Kassis J. A.,
    5. O'Farrell P.
    (1988) Two-tiered regulation of spatially patterned engrailed gene expression during Drosophila embryogenesis. Nature 322, 604–609
    OpenUrl
    1. Dougan S.,
    2. DiNardo S.
    (1992) Drosophila wingless generates cell type diversity among engrailed expressing cells. Nature 360, 347–350
    OpenUrlCrossRefPubMed
    1. Gonzalez F.,
    2. Swales L.,
    3. Bejsovec A.,
    4. Skaer H.,
    5. Martinez Arias A.
    (1991) Secretion and movement of the wingless protein in the Drosophila embryo. Mech. Dev 35, 43–54
    OpenUrlCrossRefPubMedWeb of Science
    1. Häcker U.,
    2. Lin X.,
    3. Perrimon N.
    (1997) The Drosophila sugarless gene modulates Wingless signaling and encodes an enzyme involved in polysaccharide biosynthesis. Development 124, 3565–3573
    OpenUrlAbstract
    1. Hays R.,
    2. Gibori G. B.,
    3. Bejsovec A.
    (1997) Wingless signaling generates epidermal pattern through two distinct mechanisms. Development 124, 3727–3736
    OpenUrlAbstract
    1. Ingham P. W.,
    2. Hidalgo A.
    (1993) Regulation of wingless transcription in the Drosophila embryo. Development 117, 283–291
    OpenUrlAbstract/FREE 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. Lohs-Schardin M.,
    2. Cremer C.,
    3. Nusslein-Volhard C.
    (1979) A fate map for the larval epidermis of Drosophila melanogaster: localized cuticle defects following irradiation of the blastoderm with a UV laser microbeam. Dev. Biol 73, 239–255
    OpenUrlCrossRefPubMedWeb of Science
    1. Martinez Arias A.,
    2. Baker N.,
    3. Ingham P.
    (1988) Role of the segment polarity genes in the definition and maintenance of cell states in the Drosophila embryo. Development 103, 157–170
    OpenUrlAbstract
    1. Mostov K. E.
    (1994) Transepithelial transport of immunoglobulins. Annual Review of Immunology 12, 63–84
    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. Samos C. H.,
    3. Brink M.,
    4. Willert K.,
    5. Cadigan K. M.,
    6. Fish M.,
    7. Rulifson E.
    (1997) Cell culture and whole animal approaches to understanding signaling by Wnt proteins in Drosophila. Cold Spring Harbor Symp. Quant. Biol 62, 185–190
    OpenUrlAbstract/FREE Full Text
    1. Nusse R.,
    2. Varmus H. E.
    (1992) Wnt genes. Cell 69, 1073–1087
    OpenUrlCrossRefPubMedWeb of Science
    1. Nusslein-Volhard C.,
    2. Wieschaus E.
    (1980) Mutations affecting segment number and polarity in Drosophila. Nature 287, 795–801
    OpenUrlCrossRefPubMedWeb of Science
    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. Parkin N. T.,
    2. Kitajewski J.,
    3. Varmus H. E.
    (1993) Activity of Wnt-1 as a transmembrane protein. Genes Dev 7, 2181–2193
    OpenUrlAbstract/FREE Full Text
    1. Peifer M.,
    2. Rauskolb C.,
    3. Williams M.,
    4. Riggleman B.,
    5. Wieschaus E.
    (1991) The segment polarity gene armadillo affects the wingless signalling pathway in both embryonic and adult pattern formation. Development 111, 1028–1043
    OpenUrl
    1. Reichsman F.,
    2. 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. Riese J.,
    2. Yu X.,
    3. Munnerlyn A.,
    4. Eresh S.,
    5. Hsu S.-C.,
    6. Grosschedl R.,
    7. Bienz M.
    (1997) LEF-1, a nuclear factor coordinating signalling inputs from wingless and decapentaplegic. Cell 88, 777–787
    OpenUrlCrossRefPubMedWeb of Science
    1. Riggleman B.,
    2. Schedl P.,
    3. Wieschaus E.
    (1990) Spatial expression of the Drosophila segment polarity gene armadillo is post-transcriptionally regulated by wingless. Cell 63, 549–560
    OpenUrlCrossRefPubMedWeb of Science
    1. Rijsewijk F.,
    2. Schuermann M.,
    3. Wagenaar E.,
    4. Parren P.,
    5. Weigel D.,
    6. Nusse R.
    (1987) The Drosophila homologue of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless. Cell 50, 647–657
    OpenUrl
    1. Rodman J. S.,
    2. Mercer R. W.,
    3. Stahl P. D.
    (1990) Endocytosis and transcytosis. Current Opinion in Cell Biology 2, 664–72
    OpenUrlCrossRefPubMed
    1. Sampedro J.,
    2. Johnston P.,
    3. Lawrence P. A.
    (1993) A role for wingless in the segmental gradient of Drosophila?. Development 117, 677–687
    OpenUrlAbstract
    1. Sharma R. P.,
    2. Chopra V. L.
    (1976) Effects of the wingless (wg1) mutation on wing and haltere development in Drosophila melanogaster. Dev. Biol 48, 461–465
    OpenUrlCrossRefPubMedWeb of Science
    1. Stein D.,
    2. Roth S.,
    3. Vogelsang E.,
    4. Nusslein-Volhard C.
    (1991) The polarity of the dorsoventral axis in the Drosophila embryo is defined by an extracellular signal. Cell 65, 725–735
    OpenUrlCrossRefPubMedWeb of Science
    1. Tautz D.,
    2. Pfeifle C.
    (1989) 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 98, 81–85
    OpenUrlCrossRefPubMedWeb of Science
    1. Tiong S. Y. K.,
    2. Nash D.
    (1990) Genetic analysis of the adenosine3(Gart) region of the second chromosome in Drosophila melanogaster. Genetics 124, 889–897
    OpenUrlAbstract/FREE Full Text
    1. van de Wetering M.,
    2. Cavallo R.,
    3. Dooijes D.,
    4. van Beest M.,
    5. van Es J.,
    6. Loureiro J.,
    7. Ypma A.,
    8. Hursh D.,
    9. Jones T.,
    10. Bejsovec A.,
    11. et al.
    (1997) Armadillo co-activates transcription driven by the product of the Drosophila segment polarity gene dTCF. Cell 88, 789–799
    OpenUrlCrossRefPubMedWeb of Science
    1. van den Heuvel M.,
    2. Harryman-Samos C.,
    3. Klingensmith J.,
    4. Perrimon N.,
    5. Nusse R.
    (1994) Mutations in the segment polarity genes wingless and porcupine impair secretion of the wingless protein. EMBO J 12, 5293–5302
    OpenUrl
    1. van den Heuvel M.,
    2. Nusse R.,
    3. Johnston P.,
    4. Lawrence P. A.
    (1989) Distribution of the wingless gene product in Drosophila embryos: a protein involved in cell-cell communication. Cell 59, 739–749
    OpenUrlCrossRefPubMedWeb of Science
    1. van der Bliek A. M.,
    2. Meyerowitz E. M.
    (1991) Dynamin-like protein encoded by the Drosophila shibire gene associated with vesicular traffic. Nature 351, 411–414
    OpenUrlCrossRefPubMedWeb of Science
    1. Yoffe K. B.,
    2. Manoukian A. S.,
    3. Wilder E. L.,
    4. Brand A. S.,
    5. Perrimon N.
    (1995) Evidence for engrailed -independent wingless autoregulation in Drosophila. Dev. Biol 170, 636–650
    OpenUrlCrossRefPubMed
    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
Back to top

 Download PDF

Email
JOURNAL ARTICLES
Functional analysis of Wingless reveals a link between intercellular ligand transport and dorsal-cell-specific signaling
H.A. Dierick, A. Bejsovec
Development 1998 125: 4729-4738;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Alerts

Article navigation

Other journals from The Company of Biologists

Advertisement

A new society for regenerative biologists

Kenneth Poss and Elly Tanaka announce the launch of the International Society for Regenerative Biology (ISRB), which will promote research and education in the field of regenerative biology.

Upcoming special issue: call for papers

The Immune System in Development and Regeneration
Guest editors: Florent Ginhoux and Paul Martin
Submission deadline: 1 September 2021
Publication: Spring 2022

The special issue welcomes Review articles as well as Research articles, and will be widely promoted online and at key global conferences.

An interview with Cagney Coomer

Over a virtual chat, we spoke to Cagney Coomer about her experiences in the lab, the classroom and the community centre, and why she thinks outreach and role models are vital to science.

Development presents...

Our successful webinar series continues into 2021, with early-career researchers presenting their papers and a chance to virtually network with the developmental biology community afterwards. Here, Michèle Romanos talks about her new preprint, which mixes experimentation in quail embryos and computational modelling to understand how heterogeneity in a tissue influences cell rate.

Save your spot at our next session:

10 March
Time: 9:00 (GMT)
Chaired by: Thomas Lecuit

Join our mailing list to receive news and updates on the series.