Advertisement
JOURNAL ARTICLES
A hierarchy of cross-regulation involving Notch, wingless, vestigial and cut organizes the dorsal/ventral axis of the Drosophila wing
C.J. Neumann, S.M. Cohen
Development 1996 122: 3477-3485;

Summary

Short-range interaction between dorsal and ventral cells establishes an organizing center at the dorsal/ventral compartment boundary that controls growth and patterning of the wing. We report here that the dorsal/ventral organiser is built though a hierarchy of regulatory interactions involving the Notch and wingless signal transduction pathways and the vestigial gene. wingless and vestigial are activated in cells adjacent to the dorsal/ventral boundary by a Notch-dependent signal. vestigial is initially expressed under control of an early dorsal/ventral boundary enhancer that does not depend on wingless activity. Similarly, activation of wingless does not require vestigial function, showing that wingless and vestigial are parallel targets of the Notch pathway. Subsequently, vestigial is expressed in a broad domain that fills the wing pouch. This second phase of vestigial expression depends on Wingless function in cells at the dorsal/ventral boundary. In addition, the Notch and Wingless pathways act synergistically to regulate expression of cut in cells at the dorsal/ventral boundary. Thus Wingless can act locally, in combination with Notch, to specify cell fates, as well as at a distance to control vestigial expression. These results suggest that secreted Wingless protein mediates both long-range and short-range patterning activities of the dorsal/ventral boundary.

Reference

    1. Agrawal N.,
    2. Kango M.,
    3. Mishra A.,
    4. Sinha P.
    (1995) Neoplastic transformation and aberrant cell-cell interactions in genetic mosaics of lethal(2) giant larvae (lgl), a tumor suppressor gene of Drosophila. Dev. Biol 172, 218–229
    OpenUrlCrossRefPubMedWeb of Science
    1. Axelrod J. D.,
    2. Matsuno K.,
    3. Artavanis-Tsakonas S.,
    4. Perrimon N.
    (1996) Interaction between wingless and Notch signaling pathways mediated by Dishevelled. Science 271, 1826–1832
    OpenUrlAbstract/FREE Full Text
    1. Bailey A. M.,
    2. Posakony J. W.
    (1995) Suppressor of Hairless directly activates transcription of Enhancer of split Complex genes in response to Notch receptor activity. Genes Dev 9, 2609–2622
    OpenUrlAbstract/FREE Full Text
    1. Basler K.,
    2. Struhl G.
    (1994) Compartment boundaries and the control of Drosophila limb pattern by hedgehog protein. Nature 368, 208–214
    OpenUrlCrossRefPubMedWeb of Science
    1. Bejsovec A.,
    2. Martinez-Arias A.
    (1991) Roles of wingless in patterning of the larval epidermis of Drosophila. Development 113, 471–485
    OpenUrlAbstract
    1. Blair S. S.
    (1992) shaggy (zeste-white 3) and the formation of supernumerary Bristle precursors in the developing wing blade of Drosophila. Dev. Biol 152, 263–278
    OpenUrlCrossRefPubMedWeb of Science
    1. Blair S. S.
    (1993) Mechanisms of compartment formation: Evidence that non-proliferating cells do not play a critical role in defining the D/V lineagerestriction in the developing wing of Drosophila. Development 119, 339–351
    OpenUrlAbstract
    1. Blair S. S.
    (1994) A role for the segment polarity gene shaggy-zeste white 3 in the specification of regional identity in the developing wing of Drosophila. Dev. Biol 162, 229–244
    OpenUrlCrossRefPubMedWeb of Science
    1. Blair S. S.
    (1995) Compartments and appendage development in Drosophila. BioEssays 17, 299–309
    OpenUrlCrossRefPubMedWeb of Science
    1. Blair S. S.,
    2. Brower D. L.,
    3. Thomas J. B.,
    4. Zavortink M.
    (1994) The role of apterous in the control of dorsoventral compartmentalization and PS integrin gene expression in the developing wing of Drosophila. Development 120, 1805–1815
    OpenUrlAbstract
    1. Brook W. J.,
    2. Cohen S. M.
    (1996) Antagonistic interactions between Wingless and Decapentaplegic responsible for dorsal ventral pattern in the Drosophila leg. Science 273, 1373–1377
    OpenUrlAbstract
    1. Campbell S. D.,
    2. Inamdar M.,
    3. Rodriguez V.,
    4. Raghavan V.,
    5. Palazzolo M.,
    6. Chovnick A.
    (1992) The scalloped gene encodes a novel evolutionarily conserved transcription factor requires for sensory organ differentiation in Drosophila. Genes Dev 6, 367–379
    OpenUrlAbstract/FREE Full Text
    1. Capdevila J.,
    2. Guerrero I.
    (1994) Targeted expression of the signalling molecule decapentaplegic induces pattern duplications and growth alterations in Drosophila wings. EMBO J 13, 4459–4468
    OpenUrlPubMedWeb of Science
    1. Couso J. P.,
    2. Bate M.,
    3. Martinez Arias A.
    (1993) A wingless- dependent polar coordinate system in the imaginal discs of Drosophila. Science 259, 484–489
    OpenUrlAbstract/FREE Full Text
    1. Couso J. P.,
    2. Knust E.,
    3. Martinez Arias A.
    (1995) Serrate and wingless in Drosophila wing development. Current Biology 5, 1437–1448
    OpenUrlCrossRefPubMedWeb of Science
    1. De Celis J. F.,
    2. Garcia Bellido A.
    (1994) Roles of the Notch gene in Drosophila wing morphogenesis. Mech. Devel 46, 109–122
    OpenUrlCrossRefPubMedWeb of Science
    1. De Celis J. F.,
    2. Garcia-Bellido A.,
    3. Bray S. J.
    (1996) Activation and function of Notch at the dorsal-ventral boundary of the wing imaginal disc. Development 122, 359–369
    OpenUrlAbstract
    1. Diaz-Benjumea F. J.,
    2. Cohen S. M.
    (1993) Interaction between dorsal and ventral cells in the imaginal disc directs wing development in Drosophila. Cell 75, 741–752
    OpenUrlCrossRefPubMedWeb of Science
    1. Diaz-Benjumea F. J.,
    2. Cohen S. M.
    (1995) Serrate signals through Notch to establish a Wingless-dependent organizer at the dorsal/ventral compartment boundary of the Drosophila wing. Development 121, 4215–4225
    OpenUrlAbstract
    1. Doherty D.,
    2. Fenger G.,
    3. Younger-Shepherd S.,
    4. Jan L.-Y.,
    5. Jan Y.-N.
    (1996) Dorsal and ventral cells respond differently to the Notch ligands Delta and Serrate during Drosophila wing development. Genes Dev 10, 421–434
    OpenUrlAbstract/FREE Full Text
    1. Fehon R. G.,
    2. Kooh P. J.,
    3. Rebay I.,
    4. Regan C. L.,
    5. Xu T.,
    6. Muskavitch M. A. T.,
    7. Artavanis-Tsakonas S.
    (1990) Molecular interactions between the protein products of the neurogenic loci Notch and Delta, two EGF-homolgous genes in Drosophila. Cell 61, 523–534
    OpenUrlCrossRefPubMedWeb of Science
    1. Fortini M. E.,
    2. Artavanis-Tsakonas S.
    (1994) The Suppressor of Hairless protein participates in Notch receptor signalling. Cell 79, 273–282
    OpenUrlCrossRefPubMedWeb of Science
    1. García-Bellido A.,
    2. Ripoll P.,
    3. Morata G.
    (1973) Developmental compartmentalisation of the wing disk of Drosophila. Nature New Biol 245, 251–253
    OpenUrlCrossRefPubMedWeb of Science
    1. González F.,
    2. Swales L.,
    3. Bejsovec A.,
    4. Skaer H.,
    5. Martinez-Arias A.
    (1991) Secretion and movement of the wingless protein in the epidermis of the Drosophila embryo. Mech. Dev 35, 43–54
    OpenUrlCrossRefPubMedWeb of Science
    1. Guillen I.,
    2. Mullor J. L.,
    3. Capdevilla J.,
    4. Sanchez-Herrero E.,
    5. Morata G.,
    6. Guerrero I.
    (1995) The function of engrailed and the specification of Drosophila wing pattern. Development 121, 3447–3456
    OpenUrlAbstract
    1. Hoppler S.,
    2. Bienz M.
    (1995) Two different thresholds of wingless signalling with distinct developmental consequences in the Drosophila midgut. EMBO J 14, 5016–5026
    OpenUrlPubMed
    1. Ingham P. W.,
    2. Fietz M. J.
    (1995) Quantitative effects of hedgehog and decapentaplegic activity on the patterning of the Drosophila wing. Current Biology 5, 432–440
    OpenUrlCrossRefPubMedWeb of Science
    1. Irvine K.,
    2. Wieschaus E.
    (1994) fringe, a boundary specific signallingmolecule, mediates interactions between dorsal and ventral cells during Drosophila wing development. Cell 79, 595–606
    OpenUrlCrossRefPubMedWeb of Science
    1. James A. J.,
    2. Bryant P. J.
    (1981) Mutations causing pattern deficiencies and duplications in the wing imaginal disk of Drosophila melanogaster. Devel. Biol 85, 39–54
    OpenUrlCrossRefPubMedWeb of Science
    1. Jack J.,
    2. Dorsett D.,
    3. Delotto Y.,
    4. Liu S.
    (1991) Expression of the cut locus in the Drosophila wing margin is required for cell type specification and is regulated by a distant enhancer. Development 113, 735–747
    OpenUrlAbstract
    1. Jue S. F.,
    2. Bradley R. S.,
    3. Rudnicki J. A.,
    4. Varmus H. E.,
    5. Brown A. M.
    (1992) The mouse Wnt-1 gene can act via a paracrine mechanism in transformation of mammary epithelial cells. Mol Cell Biol 12, 321–8
    OpenUrlAbstract/FREE Full Text
    1. Kassis J. A.,
    2. Noll E.,
    3. Vansickle E.P.,
    4. Odenwald W.F.,
    5. Perrimon N.
    (1992) Altering the insertional specificity of a Drosophila transposable element. Proc. Natl. Acad. Sci. USA 89, 1919–1923
    OpenUrlAbstract/FREE Full Text
    1. Kim J.,
    2. Irvine K. D.,
    3. Carroll S. B.
    (1995) Cell recognition, signal induction and symmetrical gene activation at the dorsal/ventral boundary of the developing Drosophila wing. Cell 82, 795–802
    OpenUrlCrossRefPubMedWeb of Science
    1. Klingensmith J.,
    2. Nusse R.,
    3. Perrimon N.
    (1994) The Drosophila segment polarity gene dishevelled encodes a novel protein required for response to the wingless signal. Genes Dev 8, 118–130
    OpenUrlAbstract/FREE Full Text
    1. Lawrence P. A.,
    2. Morata G.
    (1994) Homeobox genes: their function in Drosophila segmentation and pattern formation. Cell 78, 181–189
    OpenUrlCrossRefPubMedWeb of Science
    1. Lawrence P. A.,
    2. Bodmer R.,
    3. Vincent J. P.
    (1995) Segmental patterning of heart mesoderm in Drosophila. Development 121, 4303–4308
    OpenUrlAbstract
    1. Lecourtois M.,
    2. Schweisguth F.
    (1995) The neurogenic Suppressor of Hairless DNA-binding protein mediates the transcriptional activation of the Enhancer of split complex genes triggered by Notch signaling. Genes Dev 9, 2598–2608
    OpenUrlAbstract/FREE Full Text
    1. Lecuit T.,
    2. Brook W. J.,
    3. Ng M.,
    4. Calleja M.,
    5. Sun H.,
    6. Cohen S. M.
    (1996) Two distinct mechanisms for long-range patterning by Decapentaplegic in the Drosophila wing. Nature 381, 387–393
    OpenUrlCrossRefPubMedWeb of Science
    1. Morata G.,
    2. Lawrence P. A.
    (1977) The development of wingless, a homeotic mutation of Drosophila. Devel. Biol 56, 227–240
    OpenUrlCrossRefPubMedWeb of Science
    1. Nellen D.,
    2. Burke R.,
    3. Struhl G.,
    4. Basler K.
    (1996) Direct and long-range action of a Dpp morphogen gradient. Cell 85, 357–368
    OpenUrlCrossRefPubMedWeb of Science
    1. Neumann C. J.,
    2. Cohen S. M.
    (1996) Distinct mitogenic and cell fate specification functions of wingless in different regions of the wing. Development 122, 1781–1789
    OpenUrlAbstract
    1. Ng M.,
    2. Diaz-Benjumea F. J.,
    3. Vincent J.-P.,
    4. Wu J.,
    5. Cohen S. M.
    (1996) Specification of the wing primordium in Drosophila. Nature 381, 316–319
    OpenUrlCrossRefPubMed
    1. Noordermeer J.,
    2. Klingensmith J.,
    3. Perrimon N.,
    4. Nusse R.
    (1994) dishevelled and armadillo act in the Wingless signalling pathway in Drosophila. Nature 367, 80–83
    OpenUrlCrossRefPubMedWeb of Science
    1. Phillips R.,
    2. Whittle J. R. S.
    (1993) wingless expression mediates determination of peripheral nervous system elements in late stages of Drosophila wing disc development. Development 118, 427–438
    OpenUrlAbstract
    1. Rebay I.,
    2. Fleming R. J.,
    3. Fehon R. G.,
    4. Cherbas L.,
    5. Cherbas P.,
    6. Artavanis-Tsakonas S.
    (1991) Specific EGF repeats of Notch mediate interactions with Delta and Serrate: implications for Notch as a multifunctional receptor. Cell 67, 687–699
    OpenUrlCrossRefPubMedWeb of Science
    1. Rulifson E. J.,
    2. Blair S. S.
    (1995) Notch regulates wingless expression and is not required for reception of the paracrine wingless signal during wing margin neurogenesis in Drosophila. Development 121, 2813–2824
    OpenUrlAbstract
    1. Sanicola M.,
    2. Sekelsky J. S. E.,
    3. Gelbart W. M.
    (1995) Drawing a stripe in Drosophila imaginal disks: negative regulation of decapentaplegic and patched expression by engrailed. Genetics 139, 745–756
    OpenUrlAbstract/FREE Full Text
    1. Schellenbarger D. L.,
    2. Mohler J. D.
    (1978) Temperature sensitive periods and autonomy of pleiotropic effects of l(1)N ts, a conditional Notch lethal in Drosophila. Dev. Biol 62, 432–446
    OpenUrlCrossRefPubMedWeb of Science
    1. Schweisguth F.
    (1995) Suppressor of Hairless is required for signal receptionduring lateral inhibition in the Drosophila pupal notum. Development 121, 1875–1884
    OpenUrlAbstract
    1. Siegfried E.,
    2. Wilder E.,
    3. Perrimon N.
    (1994) Components of wingless signalling in Drosophila. Nature 376, 76–80
    OpenUrl
    1. Simmonds A. J.,
    2. Brook W. J.,
    3. Cohen S. M.,
    4. Bell J. B.
    (1995) Distinguishable functions for engrailed and invected in anterior-posterior patterning in the Drosophila wing. Nature 376, 424–427
    OpenUrlCrossRefPubMedWeb of Science
    1. Simpson P.,
    2. Lawrence P. A.,
    3. Maschat F.
    (1981) Clonal analysis of two wing-scalloping mutants of Drosophila. Dev. Biol 84, 206–211
    OpenUrlCrossRefPubMed
    1. Simpson P.,
    2. El Messal M.,
    3. Moscoso del Prado J.,
    4. Ripoll P.
    (1988) Stripes of positional homologies across the wing blade of Drosophila melanogaster. Development 103, 391–401
    OpenUrlAbstract
    1. Struhl G.,
    2. Fitzgerald K.,
    3. Greenwald I.
    (1993) Intrinsic activity of the Lin-12 and Notch intracellular domains in vivo. Cell 74, 331–345
    OpenUrlCrossRefPubMedWeb of Science
    1. Tabata T.,
    2. Kornberg T.
    (1994) Hedgehog is a signalling protein with a key role in patterning Drosophila imaginal discs. Cell 76, 89–102
    OpenUrlCrossRefPubMedWeb of Science
    1. Tabata T.,
    2. Schwartz C.,
    3. Gustavson E.,
    4. Ali Z.,
    5. Kornberg T. B.
    (1995) Creating a Drosophila wing de novo: the role of engrailed and the compartment border hypothesis. Development 121, 3359–3369
    OpenUrlAbstract
    1. Theisen H.,
    2. Purcell J.,
    3. Bennett M.,
    4. Kansagara D.,
    5. Syed A.,
    6. Marsh J. L.
    (1994) dishevelled is required during wingless signalling to establish both cell polarity and cell identity. Development 120, 347–360
    OpenUrlAbstract
    1. Treisman J. E.,
    2. Rubin G. M.
    (1995) wingless inhibits morphogenetic furrow movement in the Drosophila eye disc. Development 121, 3519–3527
    OpenUrlAbstract
    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. Vincent J. P.,
    2. Lawrence P.
    (1994) Drosophila wingless sustains engrailed expression only in adjoining cells: evidence from mosaic embryos. Cell 77, 909–915
    OpenUrlCrossRefPubMedWeb of Science
    1. Williams J. A.,
    2. Paddock S. W.,
    3. Carroll S. B.
    (1993) Pattern formation in a secondary field: a hierarchy of regulatory genes subdivides the developing Drosophila wing disc into discrete subregions. Development 117, 571–584
    OpenUrlAbstract
    1. Williams J. A.,
    2. Paddock S. W.,
    3. Vorwerk K.,
    4. Carroll S. B.
    (1994) Organization of wing formation and induction of a wing-patterning gene at the dorsal/ventral compartment boundary. Nature 368, 299–305
    OpenUrlCrossRefPubMed
    1. Xu T.,
    2. Rubin G. M.
    (1993) Analysis of genetic mosaics in developing and adult Drosophila tissues. Development 117, 1223–1237
    OpenUrlAbstract
    1. Yanagawa S.-I.,
    2. van Leeuwen F.,
    3. Wodarz A.,
    4. Klingensmith J.,
    5. Nusse R.
    (1995) The Dishevelled protein is modified by Wingless signaling in Drosophila. Genes Dev 9, 1087–1097
    OpenUrlAbstract/FREE Full Text
    1. Zecca M.,
    2. Basler K.,
    3. Struhl G.
    (1995) Sequential organizing activities of engrailed, hedgehog and decapentaplegic in the Drosophila wing. Development 121, 2265–2278
    OpenUrlAbstract
Back to top

 Download PDF

Email
JOURNAL ARTICLES
A hierarchy of cross-regulation involving Notch, wingless, vestigial and cut organizes the dorsal/ventral axis of the Drosophila wing
C.J. Neumann, S.M. Cohen
Development 1996 122: 3477-3485;
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

Kathryn Virginia Anderson (1952-2020)

Developmental geneticist Kathryn Anderson passed away at home on 30 November 2020. Tamara Caspary, a former postdoc and friend, remembers Kathryn and her remarkable contribution to developmental biology.

Zooming into 2021

In a new Editorial, Editor-in-Chief James Briscoe and Executive Editor Katherine Brown reflect on the triumphs and tribulations of the last 12 months, and look towards a hopefully calmer and more predictable year.

Read & Publish participation extends worldwide

Over 60 institutions in 12 countries are now participating in our Read & Publish initiative. Here, James Briscoe explains what this means for his institution, The Francis Crick Institute. Find out more and view our full list of participating institutions.

Upcoming special issues

Imaging Development, Stem Cells and Regeneration
Submission deadline: 30 March 2021
Publication: mid-2021

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

Both special issues welcome Review articles as well as Research articles, and will be widely promoted online and at key global conferences.

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. Sign up to join our next session:

10 February
Time: 13:00 (GMT)
Chaired by: preLights