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.

  • Letter
  • Published:

An activated Notch receptor blocks cell-fate commitment in the developing Drosophila eye

Abstract

THE Notch locus of Drosophila melanogaster encodes a 2,703-amino-acid transmembrane protein required for a variety of developmental processes, including neurogenesis, oogenesis and ommatidial assembly1,2. The Notch protein contains a large extracellular domain of 36 epidermal growth factor-like repeats as well as three Notch/Lin-12 repeats and an intracellular domain with 6 CdclO/ ankyrin repeats, motifs that are highly conserved in several vertebrate Notch homologues3–9. Truncation of the extracellular domain of the Drosophila Notch protein produces an activated receptor, as judged by its ability to cause phenotypes similar to gain-of-function alleles or duplications of the Notch locus10. Equivalent truncations of vertebrate Notch-related proteins have been associated with malignant neoplasms and other developmental abnormalities8,11–13. We present here an analysis of activated Notch function at single-cell resolution in the Drosophila compound eye. We find that overexpression of full-length Notch in defined cell types has no apparent effects but that overexpression of activated Notch in the same cells transiently blocks their proper cell-fate commitment, causing them either to adopt incorrect cell fates or to differentiate incompletely. Moreover, an activated Notch protein lacking the transmembrane domain is translocated to the nucleus, raising the possibility that Notch may participate directly in nuclear events.

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

Access options

Buy this article

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

Similar content being viewed by others

References

  1. Artavanis-Tsakonas, S. & Simpson, P. Trends Genet. 7, 403–408 (1991).

    Article  CAS  PubMed  Google Scholar 

  2. Greenwald, I. & Rubin, G. M. Cell 68, 271–281 (1992).

    Article  CAS  PubMed  Google Scholar 

  3. Wharton, K. A., Johansen, K. M., Xu, T. & Artavanis-Tsakonas, S. Cell 43, 567–581 (1985).

    Article  CAS  PubMed  Google Scholar 

  4. Kidd, S., Kelley, M. R. & Young, M. W. Molec. cell. Biol. 6, 3094–3108 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Coffman, C., Harris, W. & Kintner, C. Science 249, 1438–1441 (1990).

    Article  ADS  CAS  PubMed  Google Scholar 

  6. Weinmaster, G., Roberts, V. J. & Lemke, G. Development 113, 199–205 (1991).

    CAS  PubMed  Google Scholar 

  7. Franco del Amo, F. et al. Development 115, 737–744 (1992).

    CAS  Google Scholar 

  8. Ellisen, L. W. et al. Cell 66, 649–661 (1991).

    Article  CAS  PubMed  Google Scholar 

  9. Stifani, S., Blaumueller, C. M., Redhead, N. J., Hill, R. E. & Artavanis-Tsakonas, S. Nature Genet. 2, 119–127 (1992).

    Article  CAS  PubMed  Google Scholar 

  10. Rebay, I., Fehon, R. G. & Artavanis-Tsakonas, S. Cell 74, 319–329 (1993).

    Article  CAS  PubMed  Google Scholar 

  11. Robbins, J., Blondel, B. J., Gallahan, D. & Callahan, R. J. Virol. 66, 2594–2599 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Jhappan, C. et al. Genes Dev. 6, 345–355 (1992).

    Article  CAS  PubMed  Google Scholar 

  13. Coffman, C. R., Skoglund, P., Harris, W. A. & Kintner, C. R. Cell 73, 659–671 (1993).

    Article  CAS  PubMed  Google Scholar 

  14. Tomlinson, A., Bowtell, D. D. L., Hafen, E. & Rubin, G. M. Cell 51, 143–150 (1987).

    Article  CAS  PubMed  Google Scholar 

  15. Bowtell, D. D. L., Kimmel, B. E., Simon, M. A. & Rubin, G. M. Proc. natn. Acad. Sci. U.S.A. 86, 6245–6249 (1989).

    Article  ADS  CAS  Google Scholar 

  16. Fehon, R. G., Johansen, K., Rebay, I. & Artavanis-Tsakonas, S. J. Cell Biol. 113, 657–669 (1991).

    Article  CAS  PubMed  Google Scholar 

  17. Heitzler, P. & Simpson, P. Cell 64, 1083–1092 (1991).

    Article  CAS  PubMed  Google Scholar 

  18. Mlodzik, M., Hiromi, Y., Weber, U., Goodman, C. S. & Rubin, G. M. Cell 60, 211–224 (1990).

    Article  CAS  PubMed  Google Scholar 

  19. Heberlein, U., Mlodzik, M. & Rubin, G. M. Development 112, 703–712 (1991).

    CAS  PubMed  Google Scholar 

  20. Rubin, G. M. Trends Genet. 7, 372–377 (1991).

    Article  CAS  PubMed  Google Scholar 

  21. Tomlinson, A. & Ready, D. F. Devl Biol. 123, 264–275 (1987).

    Article  CAS  Google Scholar 

  22. Reinke, R. & Zipursky, S. L. Cell 55, 321–330 (1988).

    Article  CAS  PubMed  Google Scholar 

  23. Carthew, R. W. & Rubin, G. M. Cell 63, 561–577 (1990).

    Article  CAS  PubMed  Google Scholar 

  24. Smoller, D. et al. Genes Dev. 4, 1688–1700 (1990).

    Article  CAS  PubMed  Google Scholar 

  25. Delidakis, C., Preiss, A., Hartley, D. A. & Artavanis-Tsakonas, S. Genetics 129, 803–823 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Bier, E., Ackerman, L., Barbel, S., Jan, L. & Jan, Y. N. Science 240, 913–916 (1988).

    Article  ADS  CAS  PubMed  Google Scholar 

  27. Robinow, S. & White, K. J. Neurobiol. 22, 443–461 (1991).

    Article  CAS  PubMed  Google Scholar 

  28. Fortini, M. E., Simon, M. A. & Rubin, G. M. Nature 355, 559–561 (1992).

    Article  ADS  CAS  PubMed  Google Scholar 

  29. Fortini, M. E. & Rubin, G. M. Genes Dev. 4, 444–463 (1990).

    Article  CAS  PubMed  Google Scholar 

  30. Gaul, U., Mardon, G. & Rubin, G. M. Cell 68, 1007–1019 (1992).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fortini, M., Rebay, I., Caron, L. et al. An activated Notch receptor blocks cell-fate commitment in the developing Drosophila eye. Nature 365, 555–557 (1993). https://doi.org/10.1038/365555a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/365555a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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