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.

  • Article
  • Published:

Schnurri mediates Dpp-dependent repression of brinker transcription

Abstract

Signalling by Decapentaplegic (Dpp), a member of the TGFβ superfamily of signalling molecules, controls many aspects of Drosophila development by activating and repressing target genes. Several essential components of the Dpp signalling pathway have been identified, including the Dpp receptors Punt and Thick veins (Tkv) as well as the cytoplasmic mediators Mad and Medea. For target genes to be activated, Dpp signalling must suppress transcription of a repressor encoded by the brinker (brk) gene. Here we show that Schnurri (Shn), a large zinc-finger protein, is essential for Dpp-mediated repression of brk transcription; in contrast, Shn is not required for target-gene activation. Thus, the Dpp signalling pathway bifurcates, downstream of the signal-mediating SMAD proteins, into a Shn-dependent pathway leading to brk repression and a Shn-independent pathway leading to gene activation. The existence of several Shn-like proteins in vertebrates and the observation that Brk functions in BMP signalling in Xenopus indicates that a similar regulatory cascade may be conserved in higher organisms.

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

Figure 1: Shn is required for Dpp-mediated repression of brk transcription.
Figure 2: Removal of brk restores Dpp-responsiveness to shn-mutant embryos.
Figure 3: shn function is dispensable for activation of the Dpp target gene sal.
Figure 4: shn function is dispensable for activation of the Dpp-dependent quadrant enhancer of vg.
Figure 5: Model for the function of Shn in Dpp signalling.

Similar content being viewed by others

References

  1. Raftery, L. A. & Sutherland, D. J. TGF-β family signal transduction in Drosophila development: from Mad to Smads. Dev. Biol. 210, 251–268 ( 1999).

    Article  CAS  Google Scholar 

  2. Massagué, J. TGF-β signal transduction. Annu. Rev. Biochem. 67, 753–791 (1998).

    Article  Google Scholar 

  3. Massagué, J. & Wotton, D. Transcriptional control by the TGF-β/Smad signaling system. EMBO J. 19, 1745–1754 (2000).

    Article  Google Scholar 

  4. Campbell, G. & Tomlinson, A. Transducing the Dpp morphogen gradient in the wing of Drosophila: Regulation of Dpp targets by brinker. Cell 96, 553– 562 (1999).

    Article  CAS  Google Scholar 

  5. Jaźwińska, A., Kirov, N., Wieschaus, E., Roth, S. & Rushlow, C. The Drosophila gene brinker reveals a novel mechanism of Dpp target gene regulation. Cell 96, 563–573 (1999).

    Article  Google Scholar 

  6. Minami, M., Kinoshita, N., Kamoshida, Y., Tanimoto, H. & Tabata, T. brinker is a target of Dpp in Drosophila that negatively regulates Dpp-dependent genes. Nature 398, 242–246 (1999).

    Article  CAS  Google Scholar 

  7. Jaźwińska, A., Rushlow, C. & Roth, S. The role of brinker in mediating the graded response to Dpp in early Drosophila embryos. Development 126, 3323–3334 (1999).

    PubMed  Google Scholar 

  8. Arora, K. et al. The Drosophila schnurri gene acts in the Dpp/TGFβ signalling pathway and encodes a transcription factor homologous to the human MBP family. Cell 81, 781– 790 (1995).

    Article  CAS  Google Scholar 

  9. Grieder, N. C., Nellen, D., Burke, R., Basler, K. & Affolter, M. schnurri is required for Drosophila Dpp signalling and encodes a zinc finger protein similar to the mammalian transcription factor PRDII-BFI. Cell 81, 791– 800 (1995).

    Article  CAS  Google Scholar 

  10. Staehling-Hampton, K., Laughon, A.S. & Hoffmann, F.M. A Drosophila protein related to the human zinc finger transcription factor PRDII/MBPI/HIV-EP1 is required for dpp signalling. Development 121, 3393– 3403 (1995).

    CAS  PubMed  Google Scholar 

  11. Burke, R. & Basler, K. Dpp receptors are autonomously required for cell proliferation in the entire developing Drosophila wing. Development 122, 2261–2269 (1996).

    CAS  PubMed  Google Scholar 

  12. Bienz, M. Induction of the endoderm in Drosophila. Sem. Cell Dev. Biol. 7, 113–119 (1996).

    Article  Google Scholar 

  13. Tsuneizumi, K. et al. Daughters against dpp modulates dpp organizing activity in Drosophila wing development. Nature 389, 627–631 (1997).

    Article  CAS  Google Scholar 

  14. Nellen, D., Burke, R., Struhl, G. & Basler, K. Direct and long-range action of a DPP morphogen gradient. Cell 85, 357–368 (1996).

    Article  CAS  Google Scholar 

  15. Lecuit, T. et al. Two distinct mechanisms for long-range patterning by decapentaplegic in the Drosophila wing. Nature 381, 387–393 (1996).

    Article  CAS  Google Scholar 

  16. Kim, J. et al. Integration of positional signals and regulation of wing formation and identity by Drosophila vestigal gene. Nature 382, 133–138.

  17. Kim, J., Hohnson, K., Chen, H. J., Carroll, S. & Laughon, A. Drosophila Mad binds to DNA and directly mediates activation of vestigial by Decapentaplegic. Nature 388, 304–308.

  18. Udagawa, Y. et al. Schnurri interacts with Mad in a Dpp-dependent manner. Genes to Cell 5, 359–370 (2000).

    Article  CAS  Google Scholar 

  19. Certel, K., Hudson, A., Carroll, S. B. & Johnson, W. A. Restricted patterning of vestigal expression in Drosophila wing imaginal discs requires synergistic activation by both Mad and the Drifter POU domain transcription factor. Development 127, 3173–3183 (2000).

    CAS  PubMed  Google Scholar 

  20. Fan, C. M. & Maniatis, T. A DNA-binding protein containing two widely separated zinc finger motifs that recognize the same DNA sequence . Genes Dev. 4, 29–42 (1990).

    Article  CAS  Google Scholar 

  21. Mitchelmore, C., Traboni, C. & Cortese, R. Isolation of two cDNAs encoding zinc finger proteins which bind to the a1-antitrypsin promoter and to the major histocompatibility complex class I enhancer. Nucleic Acids Res. 19, 141–147 (1990).

    Article  Google Scholar 

  22. Baldwin, A. S. Jr, LeClair, K. P., Singh, H. & Sharp, P. A. A large protein containing zinc finger domains bind to related sequence elements in the enhancer of the class I major histocompatibility complex and kappa immunoglobulin genes. Mol. Cell Biol. 10, 1406–1414 (1990).

    Article  CAS  Google Scholar 

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

    CAS  Google Scholar 

  24. Grieder, N. C. Involvement of the zinc finger protein encoded by the schnurri gene of Drosophila melanogaster in the signal transduction pathway of Dpp. PhD Thesis, Univ. Basel, Switzerland (1997).

    Google Scholar 

  25. Ruberte, E., Marty, T., Nellen, D., Affolter, M. & Basler, K. An absolute requirement for both the type II and type I receptors, Punt and thick veins, for Dpp signaling in vivo. Cell 80, 890–898 (1995).

    Article  Google Scholar 

  26. Martin-Bermudo, M. D., Dunin-Borkowski, O. M. & Brown, N. H. Specificity of PS integrin function during embryogenesis resides in the alpha subunit extracellular domain. EMBO J. 16, 4184–4193 (1997).

    Article  CAS  Google Scholar 

  27. Tautz, D. & Pfeifle, C. A non-radioactive in situ hybridization method for the localization of specific RNAs in Drosophila embryos reveals a translational control of the segmentation gene hunchback . Chromosoma 98, 81–85 (1989).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank R. Schuh, S. Cohen and N. Patel for antibodies, and S. Roth, C. Rushlow, A. Tomlinson, N. Brown and S. B. Carroll for flies and cDNAs. We also thank N. C. Grieder for the UAS-shn strains and C. Bazinet for comments on the manuscript. This work was supported by the Swiss National Science Foundation and by the Kantons of Basel-Stadt, Basel-Land and Zürich. During the course of this work, M.A. was a START fellow of the Swiss National Science Foundation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Markus Affolter.

Additional information

Correspondence and requests for materials should be addressed to M. A.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Marty, T., Müller, B., Basler, K. et al. Schnurri mediates Dpp-dependent repression of brinker transcription . Nat Cell Biol 2, 745–749 (2000). https://doi.org/10.1038/35036383

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/35036383

This article is cited by

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