Abstract
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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
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).
Zecca, M., Basler, K. & Struhl, G. Sequential organizing activities of engrailed, hedgehog and decapentaplegic in the Drosophila wing. Development 121, 2265–2278 (1995).
Nellen, D., Burke, R., Struhl, G. & Basler, K. Direct and long-range action of a DPP morphogen gradient. Cell 85, 357–368 (1996).
Lecuit, T. et al. Two distinct mechanisms for long-range patterning by Decapentaplegic in the Drosophila wing. Nature 381, 387–393 (1996).
Grimm, S. & Pflugfelder, G. O. Control of the gene optomotor-blind in Drosophila wing development by decapentaplegic and wingless. Science 271, 1601–1604 (1996).
de Celis, J. F., Barrio, R. & Kafatos, F. C. Agene complex acting downstream of dpp in Drosophila wing morphogenesis. Nature 381, 421–424 (1996).
Tsuneizumi, K. et al. Daughters against dpp modulates dpp organizing activity in Drosophila wing development. Nature 389, 627–631 (1997).
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).
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).
Rushlow, C., Silver, S. & Roth, S. brinker, a negative regulator of the dpp pathway. A. Conf. Dros. Res. 39, 245B (1998).
Brand, A. H. & Perrimon, N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118, 401–415 (1993).
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).
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).
Ferguson, E. L. Conservation of dorsal–ventral patterning in arthropods and chordates. Curr. Opin. Genet. Dev. 6, 424–431 (1996).
Kao, K. R. & Elinson, R. P. Dorsalization of mesoderm induction by lithium. Dev. Biol. 132, 81–90 (1989).
Graff, J. M. Embryonic patterning: To BMP or not to BMP, that is the question. Cell 89, 171–174 (1997).
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).
Brown, N. H. & Kafatos, F. C. Functional cDNA libraries from Drosophila embryos. J. Mol. Biol. 203, 425–437 (1988).
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).
Duffy, J. B., Harrison, D. A. & Perrimon, N. Identifying loci required for follicular pattening using directed mosaics. Development 125, 2263–2271 (1998).
Xu, T. & Rubin, G. M. Analysis of genetic mosaics in developing and adult Drosophila tissues. Development 117, 1223–1237 (1993).
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).
Kintner, C. & Brockes, J. P. Monoclonal antibodies identify blastemal cells derived from differentiating muscle in newt limb regeneration. Nature 308, 67–69 (1984).
Nieuwkoop, P. D. & Faber, J. Normal Table of Xenopus laevis (Garland, New York and London, (1994).
Wilson, P. A. & Melton, D. A. Mesodermal patterning by an inducer gradient depends on secondary cell–cell communication. Curr. Biol. 4, 676–686 (1994).
Hemmati-Brivanlou, A. & Melton, D. A. Inhibition of activin receptor signaling promotes neuralization in Xenopus. Cell 77, 273–281 (1994).
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).
Acknowledgements
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
Authors and Affiliations
Corresponding author
Rights 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). https://doi.org/10.1038/18451
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/18451
This article is cited by
-
Drosophila ML-DmD17-c3 cells respond robustly to Dpp and exhibit complex transcriptional feedback on BMP signaling components
BMC Developmental Biology (2019)
-
The genes expression difference between winged and wingless bird cherry-oat aphid Rhopalosiphum padi based on transcriptomic data
Scientific Reports (2019)
-
Asymmetric distribution of Spalt in Drosophila wing squamous and columnar epithelia ensures correct cell morphogenesis
Scientific Reports (2016)
-
The morphogen Decapentaplegic employs a two-tier mechanism to activate target retinal determining genes during ectopic eye formation in Drosophila
Scientific Reports (2016)
-
Dpp spreading is required for medial but not for lateral wing disc growth
Nature (2015)
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.