Skip to main content

Thank you for visiting 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.

brinker is a target of Dpp in Drosophila that negatively regulates Dpp-dependent genes


Growth and patterning of the Drosophila wing is controlled in part by the long-range organizing activities of the Decapentaplegic protein (Dpp)1,2,3,4. Dpp is synthesized by cells that line the anterior side of the anterior/posterior compartment border of the wing imaginal disc. From this source, Dpp is thought to generate a concentration gradient that patterns both anterior and posterior compartments. Among the gene targets that it regulates are optomotor blind (omb)5, spalt (sal)6, and daughters against dpp (dad)7. We report here the molecular cloning of brinker (brk), and show that brk expression is repressed by dpp. brk encodes, a protein that negatively regulates Dpp-dependent genes. Expression of brk in Xenopus embryos indicates that brk can also repress the targets of a vertebrate homologue of Dpp, bone morphogenetic protein 4 (BMP-4). The evolutionary conservation of Brk function underscores the importance of its negative role in proportioning Dpp activity.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Expression of brk is negatively controlled by dpp in the wing imaginal disc.
Figure 2: Deduced amino-acid sequence of Brk and alignment with Drosophila Dsx.
Figure 3: Phenotypes and gene expression patterns in somatic brk clones.
Figure 4: Brk can antagonize signalling by BMP-4.


  1. 1

    Capdevila, J. & Cuerrero, I. Targeted expression of the signaling molecule decapentaplegic induces pattern duplications and growth alterations in Drosophila wings. EMBO J. 13, 4459–4468 (1994).

    CAS  Article  PubMed Central  Google Scholar 

  2. 2

    Zecca, M., Basler, K. & Struhl, G. Sequential organizing activities of engrailed, hedgehog and decapentaplegic in the Drosophila wing. Development 121, 2265–2278 (1995).

    CAS  PubMed  Google Scholar 

  3. 3

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

    CAS  Article  PubMed Central  Google Scholar 

  4. 4

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

    ADS  CAS  Article  Google Scholar 

  5. 5

    Grimm, S. & Pflugfelder, G. O. Control of the gene optomotor-blind in Drosophila wing development by decapentaplegic and wingless. Science 271, 1601–1604 (1996).

    ADS  CAS  Article  Google Scholar 

  6. 6

    de Celis, J. F., Barrio, R. & Kafatos, F. C. Agene complex acting downstream of dpp in Drosophila wing morphogenesis. Nature 381, 421–424 (1996).

    ADS  CAS  Article  Google Scholar 

  7. 7

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

    ADS  CAS  Article  Google Scholar 

  8. 8

    Inoue, H. et al. Interplay of signal mediators of Decapentaplegic (Dpp): Molecular characterization of Mothers against dpp, Medea, and Daughters against dpp. Mol. Biol. Cell 9, 2145–2156 (1998).

    CAS  Article  PubMed Central  Google Scholar 

  9. 9

    Jazwinska, A., Rushlow, C. & Roth, S. brk, a component of the dpp pathway, affects patterning of the Drosophila appendages. A. Conf. Dros. Res. 39, 244A (1998).

    Google Scholar 

  10. 10

    Rushlow, C., Silver, S. & Roth, S. brinker, a negative regulator of the dpp pathway. A. Conf. Dros. Res. 39, 245B (1998).

    Google Scholar 

  11. 11

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

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12

    Sekelsky, J., Newfeld, S., Raftery, L., Chartoff, E. & Gelbart, W. Genetic characterization and cloning of Mothers against dpp, a gene required for decaptentaplegic function in Drosophila melanogaster. Genetics 139, 1347–1358 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13

    Burtis, K. C. & Baker, B. S. Drosophila doublesex gene controls somatic sexual differentiation by producing alternatively spliced mRNAs encoding related sex-specific polypeptides. Cell 56, 997–1010 (1989).

    CAS  Article  Google Scholar 

  14. 14

    Ferguson, E. L. Conservation of dorsal–ventral patterning in arthropods and chordates. Curr. Opin. Genet. Dev. 6, 424–431 (1996).

    CAS  Article  Google Scholar 

  15. 15

    Kao, K. R. & Elinson, R. P. Dorsalization of mesoderm induction by lithium. Dev. Biol. 132, 81–90 (1989).

    CAS  Article  Google Scholar 

  16. 16

    Graff, J. M. Embryonic patterning: To BMP or not to BMP, that is the question. Cell 89, 171–174 (1997).

    CAS  Article  Google Scholar 

  17. 17

    Newfeld, S. J., Chartoff, E. H., Graff, J. M., Melton, D. A. & Gelbart, W. M. Mothers against dpp encodes a conserved cytoplasmic protein required in DPP/TGF-β responsive cells. Development 122, 2099–2108 (1996).

    CAS  PubMed  Google Scholar 

  18. 18

    Brown, N. H. & Kafatos, F. C. Functional cDNA libraries from Drosophila embryos. J. Mol. Biol. 203, 425–437 (1988).

    CAS  Article  Google Scholar 

  19. 19

    Wagner-Bernholz, J. T., Wilson, C., Gibson, G., Schuh, R. & Gehring, W. J. Identification of target genes of the homeotic gene Antennapedia by enhancer detection. Genes Dev. 5, 2467–2480 (1991).

    CAS  Article  Google Scholar 

  20. 20

    Duffy, J. B., Harrison, D. A. & Perrimon, N. Identifying loci required for follicular pattening using directed mosaics. Development 125, 2263–2271 (1998).

    CAS  Google Scholar 

  21. 21

    Xu, T. & Rubin, G. M. Analysis of genetic mosaics in developing and adult Drosophila tissues. Development 117, 1223–1237 (1993).

    CAS  Google Scholar 

  22. 22

    Hemmati-Brivanlou, A. & Harland, R. M. Expression of an engrailed-related protein is induced in the anterior neural ectoderm of early Xenopus embryos. Development 106, 611–617 (1989).

    Google Scholar 

  23. 23

    Kintner, C. & Brockes, J. P. Monoclonal antibodies identify blastemal cells derived from differentiating muscle in newt limb regeneration. Nature 308, 67–69 (1984).

    ADS  CAS  Article  Google Scholar 

  24. 24

    Nieuwkoop, P. D. & Faber, J. Normal Table of Xenopus laevis (Garland, New York and London, (1994).

    Google Scholar 

  25. 25

    Wilson, P. A. & Melton, D. A. Mesodermal patterning by an inducer gradient depends on secondary cell–cell communication. Curr. Biol. 4, 676–686 (1994).

    CAS  Article  Google Scholar 

  26. 26

    Hemmati-Brivanlou, A. & Melton, D. A. Inhibition of activin receptor signaling promotes neuralization in Xenopus. Cell 77, 273–281 (1994).

    CAS  Article  Google Scholar 

  27. 27

    Blitz, I. L. & Cho, K. W. Y. Anterior neurectoderm is progressively induced during grastrulation: the role of the Xenopus homeobox gene orthodenticle. Development 121, 993–1004 (1995).

    CAS  PubMed  Google Scholar 

Download references


We thank C. Rushlow for exchanging unpublished data; T. Kornberg and J. Christian for critically reading the manuscript; H. Eguchi in Research Center for Nuclear Science and Technology for help with γ irradiation experiments; K. Niwano for technical assistance; members of T.T.'s laboratory for their help; K. Basler, S. Goto, Y. N. Jan, T. Kornberg, M. Mlodzik, S. Morimura, G. Pflugfelder, F.-A. Ramirez-Weber, F. Roth, S. Roth, G. Struhl and the Bloomington Drosophila Stock Center for fly strains; G. Pflugfelder for the Omb antibody; and M.Kirschner and S. Newfeld for BMP-4 and Mad cDNA, respectively. This work was supported by grants from the Japan Society for the Promotion of Science (Research for the Future Program) to T.T. and grants-in-aid from the Ministry of Education, Science and Culture of Japan to M.M., N.K. and T.T. M.M. is a Research Fellow of the Japan Society for the Promotion of Science.

Author information



Corresponding author

Correspondence to Tetsuya Tabata.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Minami, M., Kinoshita, N., Kamoshida, Y. et al. brinker is a target of Dpp in Drosophila that negatively regulates Dpp-dependent genes. Nature 398, 242–246 (1999).

Download citation

Further reading


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.


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