Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Fringe boundaries coincide with Notch-dependent patterning centres in mammals and alter Notch-dependent development in Drosophila

Nature Genetics volume 16, pages 283–288 (1997)Cite this article

Abstract

In both vertebrate and invertebrate development, cells are often programmed to adopt fates distinct from their neighbors. Genetic analyses in Drosophila melanogaster have highlighted the importance of cell surface and secreted proteins in these cell fate decisions. Homologues of these proteins have been identified and shown to play similar roles in vertebrate development1–5. Fringe, a novel signalling protein, has been shown to induce wing margin formation in Drosophila6. Fringe shares significant sequence homology and predicted secondary structure similarity with bacterial glycosyltransferases7. Thus, fringe may control wing development by altering glycosylation of cell surface and/or secreted molecules. Recently, two fringe genes were isolated from Xenopus laevis8. We report here the cloning and characterization of three murine fringe genes (lunatic fringe, manic fringe and radical fringe). We find in several tissues that fringe expression boundaries coincide with Notch-dependent patterning centres and with Notch-ligand expression boundaries. Ectopic expression of murine manic fringe or radical fringe in Drosophila results in phenotypes that resemble those seen in Notch mutants.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

References

  1. Parr, B.A. & McMahon, A.P. Wnt genes and vertebrate development. Curr. Opin. Genet Dev. 4, 523–528 (1994).

    Article  CAS  Google Scholar 

  2. Ingham, P.W. Signaling by hedgehog-family proteins in Drosophila and vertebrate development. Curr. Opin. Genet. Dev. 5, 492–498 (1995).

    Article  CAS  PubMed  Google Scholar 

  3. Hogan, B.L.M. Bone morphogenetic proteins: multifunctional regulators of vertebrate development. Genes Dev. 10, 1580–1394 (1996).

    Article  CAS  PubMed  Google Scholar 

  4. Lardelli, M., Williams, R. & Lendahl, U. Notch-related genes in animal development. Int. J. Dev. Biol. 39, 769–780 (1995).

    CAS  PubMed  Google Scholar 

  5. Kopan, R. & Turner, D.L., Notch pathway: democracy and aristocracy in the selection of cell fate. Curr. Opin. Neurobiol. 6, 594–601 (1996).

    Article  CAS  PubMed  Google Scholar 

  6. Irvine, K.D. & Wieschaus, E., Fringe, a boundary-specific molecule, mediates interactions between dorsal and ventral cells during. Drosophila wing development. Cell 79, 595–606 (1994).

    Article  CAS  PubMed  Google Scholar 

  7. Yuan, Y.P., Schultz, J., Mlodzik, M. & Bork, P., Fringe-like signaling molecules may be glycosyItransf erases. Cell 88, 9–11 (1997).

    Article  CAS  PubMed  Google Scholar 

  8. Wu, J.Y., Zhang, W.-J. & Rao, Y. The s jcreted product of Xenopus gene lunatic Fringe, a vertebrate signaling molecule. .Science 273, 355–358 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Conlon, R.A., Reaume, A.G. & Rossant, J. Notchl is required for the coordinate segmentation of somites. Development 121, 1533–1545 (1995).

    CAS  PubMed  Google Scholar 

  10. Bettenhausen, B., Hrabe de Angelis, M., Simon, D., Guenet, J.-L. & Gossler, A. Transient and restricted expression during mou ;e embryogenesis of DII1, a murine gene closely related to Drosophila Delta. Development 121, 2407–2418 (1995).

    CAS  PubMed  Google Scholar 

  11. Lindsell, C.E., Shawber, C.J., Boulter, J. & Weinmaster, G. Jagged: a mammalian ligand that activates Notch1. Cell 80, 909–917 (1995).

    Article  CAS  PubMed  Google Scholar 

  12. Myat, A., Henrique, D., Ish-Horowicz, D. & Lewis, J. A chick homologue of Serrate and its relationship with Notch and De ta homologues during central neurogenesis. Dev. Biol. 174, 233–247 (1996).

    Article  CAS  PubMed  Google Scholar 

  13. Shawber, C., Boulter, J., Lindsell, C.E. & Weinmaster, G. Jagged2: A serrate-like gene expressed during rat embryogenesis. Dev. Biol. 180, 370–376 (1996).

    Article  CAS  PubMed  Google Scholar 

  14. Kim, J., Irvine, K.D. & Carrol, S.B. Cell recognition, signal induction, and symmetrical gene activation at the dorsal-ventral boundary of the developing Drosophila wing. Cell 82, 795–802 (1995).

    Article  CAS  PubMed  Google Scholar 

  15. Brand, A.M. & Perrimon, N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118, 401–415 (1993).

    CAS  PubMed  Google Scholar 

  16. Hinz, U., Giebel, B. & Campos-Ortega, J.A. Tho basic-helix-loop-helix domain of Drosophila lethal of scute protein is sufficient for proneural function and activates neurogenic genes. Cell 76, 77–87 (1994).

    Article  CAS  PubMed  Google Scholar 

  17. Gustafson, K. & Boulianne, G.L. Distinct expression patterns detected within individual tissues by the GAL4 enhancer trap technique. Genome 39, 174–182 (1996).

    Article  CAS  PubMed  Google Scholar 

  18. Yen, E., Gustafson, K. & Boullianne, G.L. Green f uorescent protein as a vital marker and reporter of gene expression in Drosophila. Proc. Natl. Acad. Sci. USA 92, 7036–7040 (1995).

    Article  Google Scholar 

  19. Fleming, R.J., Scottgale, T.N., Diederich, R.J. & Artavanis-Tsakonas, S. The gene Serrate encodes a putative EGF-like transmem brane protein essential for proper ectodermal development in Drosophila melanogaster. Genes Dev. 4, 2188–2201 (1990).

    Google Scholar 

  20. Thomas, U., Speicher, S.A. & Knust, E., The Drosophila gene Serrate encodes an EGF-like transmembrane protein with a complex expression pattern in embryos and wing discs. Development 11, 749–761 (1991).

    Google Scholar 

  21. Speicher, S.A., Thomas, U., Hinz, U. & Knust, E., Serrate locus of Drosophila and its role in morphogenesis of the wing imaginal discs: control of cell proliferation. Development 120, 535–544 (1994).

    CAS  PubMed  Google Scholar 

  22. Artavanis-Tsakonas, S., Matsuno, K. & Fortini, M.E. Notch signaling. Science 268, 225–232 (1995).

    Article  CAS  PubMed  Google Scholar 

  23. Vassin, H., Bremer, K.A., Knust, E. & Campos-Ortega, J.A. The neurogenic genes Delta of Drosophila melanogaster 63, 431–440 (1987).

  24. Kopczynski, C.C., Alton, A.K., Fechtel, K., & Muskavitch, M.A.T. Delta, a Drosophila neurogenic gene, is transcriptionally complex and encodes a protein related to blood coagulation factors and epidermal growth factor of vertebrates. Genes Dev. 2, 1723–1735 (1988).

    Article  CAS  PubMed  Google Scholar 

  25. Parks, A.L. & Muskavitch, M.A.T. Delta function is required for bristle organ determination and morphogenesis in Drosophila. Dev. Biol. 157, 484–496 (1993).

    Google Scholar 

  26. Parody, T.R. & Muskavitch, M.A.T. The pleiotropic function of Delta during postembryonic development of Drosophila melanogaster. Genetics 135, 527–539 (1993).

  27. Muskavitch, M.A.T. Delta-Notch signaling and Drosophila cell fate choice. Dev. Biol. 166, 415–430 (1994).

    Article  CAS  PubMed  Google Scholar 

  28. Robey, E. et al. An activated form of Notch influences the choice between CD4 and CDS T cell lineages. Cell 87, 483–492 (1996).

    Article  CAS  PubMed  Google Scholar 

  29. Rodriguez-Esteban, C. et al. Radical fringe positions the apical ectodermal ridge at the dorsoventral boundary of the vertebrate limb. Nature 386, 360–366 (1997).

    Article  CAS  PubMed  Google Scholar 

  30. Laufer, E. et al. Expression of Radical fringe in limb-bud ectoderm regulates apical ectodermal ridge formation. Nature 386, 366–373 (1997).

    Article  CAS  PubMed  Google Scholar 

  31. de Angelis, M.H., Mclntyre II, J. & Gossler, A. Maintenance of somite borders in mice requires the Delta homologue DII1. Nature 386, 717–721 (1997).

    Article  Google Scholar 

  32. Johnston, S.H. et al. A family of mammalian fringe genes implicated in boundary determination and the Notch pathway. Development 124, 2245–2254 (1997).

    CAS  PubMed  Google Scholar 

  33. Hui, C.-C., Slusarski, D., Platt, K.A., Holmgren, R & Joyner, A.L. Expression of three mouse homologs of the Drosophila segment polarity gene cubitus interruptus, Gli, Gli-2, and Gli-3, in ectoderm- and mesoderm-derived tissues suggests multiple roles during postimplantation development. Dev. Biol. 162, 402–413 (1994).

    Article  CAS  PubMed  Google Scholar 

  34. Spradling, A.C. P-element-mediated transformation in Drosophila: A practical approach (ed. Roberts, D.B.) 175–197 (IRL Press, Oxford, 1986).

    Google Scholar 

  35. Lawrence, P.A., Johnston, P. & Morata, G. Methods of marking cells, in Drosophila: A Practical Approach, (ed. Roberts, D.B.) 229–242 (IRL Press, Oxford, 1986).

    Google Scholar 

  36. Tomlinson, A. & Ready, D.F. Cell fate in the Drosophila ommatidium. Dev. Biol. 123, 264–275 (1987).

    Google Scholar 

Download references

Author information

Author notes

  1. Brenda Cohen and Arash Bashirullah: B.C. & A.B. contributed equally to this work.

Authors and Affiliations

  1. Division of Immunology and Cancer Research, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G1X8, Canada

    Brenda Cohen, Lina Dagnino, Christine Campbell, Ching Ching Leow, Elisabeth Whiting, David Ryan, Brenda Gallic, Robert A. Phillips & Sean E. Egan

  2. Division of Endocrinology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G1X8, Canada

    Arash Bashirullah, William W. Fisher, Dawn Zinyk, Chi-chung Hui & Howard D. Lipshitz

  3. Division of Biology, California Institute of Technology, Pasadena, California, USA

    Arash Bashirullah & Howard D. Lipshitz

  4. Department of Molecular and Medical Genetics, University of Toronto, Ontario, Canada

    Ching Ching Leow, Dawn Zinyk, Chi-chung Hui, Brenda Gallic, Robert A. Phillips, Howard D. Lipshitz & Sean E. Egan

  5. Program in Developmental Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G1X8, Canada

    Gabrielle Boulianne, Chi-chung Hui, Brenda Gallic, Robert A. Phillips, Howard D. Lipshitz & Sean E. Egan

  6. Division of Neurology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G1X8, Canada

    Gabrielle Boulianne

  7. Department of Physiology, The University of Toronto, Toronto, Ontario, Canada

    Gabrielle Boulianne

  8. Division of Immunology and Cancer Research, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G1X8, Canada

    Sean E. Egan

Authors
  1. Brenda Cohen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arash Bashirullah
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lina Dagnino
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christine Campbell
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. William W. Fisher
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ching Ching Leow
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Elisabeth Whiting
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. David Ryan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dawn Zinyk
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Gabrielle Boulianne
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Chi-chung Hui
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Brenda Gallic
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Robert A. Phillips
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Howard D. Lipshitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Sean E. Egan
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Cohen, B., Bashirullah, A., Dagnino, L. et al. Fringe boundaries coincide with Notch-dependent patterning centres in mammals and alter Notch-dependent development in Drosophila. Nat Genet 16, 283–288 (1997). https://doi.org/10.1038/ng0797-283

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0797-283

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing