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Daughters against dpp modulates dpp organizing activity in Drosophila wing development

Abstract

The family of TGF-β signalling molecules play inductive roles in various developmental contexts1. One member of this family, Drosophila Decapentaplegic (Dpp)2 serves as a morphogen that patterns both the embryo3,1 and adult4,5. We have now isolated a gene, Daughters against dpp ( Dad), whose transcription is induced by Dpp. Dad shares weak homology with Drosophila Mad (Mothers against dpp)6, a protein required for transduction of Dpp signals. In contrast to Mad or the activated Dpp receptor, whose overexpression hyperactivates the Dpp signalling pathway, overexpression of Dad blocks Dpp activity. Expression of Dad together with either Mad or the activated receptor rescues phenotypic defects induced by each protein alone. Dad can also antagonize the activity of a vertebrate homologue of Dpp, bone morphogenetic protein (BMP-4; ref. 7), as evidenced by induction of dorsal or neural fate following overexpression in Xenopus embryos. We conclude that the pattern-organizing mechanism governed by Dpp involves a negative-feedback circuit in which Dpp induces expression of its own antagonist, Dad. This feedback loop appears to be conserved in vertebrate development.

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Figure 1: Dad expression is positively controlled by Dpp in the wing imaginal disc.
Figure 2: Deduced amino-acid sequence of Dad and alignment with Drosophila Mad6, human Smad1 (ref. 32) and Smad6 (ref. 15).
Figure 3: Functional interactions between Dad, tkv, and Mad in adult wings.
Figure 4: Dad and Mad effects on Omb expression.
Figure 5: Dad antagonizes BMP-4 activity in Xenopus embryos.

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Acknowledgements

We thank I. Yabe for help with the confocal microscopy, H. Eguchi for helpwith the Γ-ray irradiation, and K. Basler, Y.Hiromi, Y.-N. Jan, S. Morimura, S. Newfeld, G.Pflugfelder, A.Spradling and the Bloomington Drosophila Stock Centre for fly strains. This work was supported by grants from the Japan Society for the Promotion of Science (Research for the Future Program), from the New Energy and Industrial Technology Development Organization, and the Uehara Memorial Foundation to T.T., by grants-in-aid from the Ministry of Education, Science, Sports and Culture of Japan to T.T. and K.T., by grants from the NIH to J.L.C. and T.B.K., and from the American Heart Association to J.L.C. T.N. was the recipient of a postdoctoral fellowship from the Toyobo Biotechnology Foundation (Japan) and is currently supported by the American Heart Association, Oregon Affiliate.

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Correspondence to Tetsuya Tabata.

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Tsuneizumi, K., Nakayama, T., Kamoshida, Y. et al. Daughters against dpp modulates dpp organizing activity in Drosophila wing development. Nature 389, 627–631 (1997). https://doi.org/10.1038/39362

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