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.
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We thank C. Rushlow for exchanging unpublished data; T. Kornberg and J. Christian for critically reading the manuscript; H. Eguchi in Research Center for Nuclear Science and Technology for help with γ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.
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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
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