Abstract
In many instances during development, morphogens specify cell fates by forming concentration gradients. In the Drosophila melanogaster wing imaginal disc, Decapentaplegic (Dpp), a bone morphogenetic protein (BMP), functions as a long-range morphogen to control patterning and growth1. Dpp is secreted from a stripe of cells at the anterior-posterior compartment boundary and spreads into both compartments to generate a characteristic BMP activity gradient2,3,4,5,6. Ever since the identification of the morphogen activity of Dpp in the developing wing, the system has served as a paradigm to understand how long-range gradients are established and how cells respond to such gradients. Here we reveal the tight and direct connection of these two processes with the identification and characterization of pentagone (pent), a transcriptional target of BMP signalling encoding a secreted regulator of the pathway. Absence of pent in the wing disc causes a severe contraction of the BMP activity gradient resulting in patterning and growth defects. We show that Pent interacts with the glypican Dally to control Dpp distribution and provide evidence that proper establishment of the BMP morphogen gradient requires the inbuilt feedback loop embodied by Pent.
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Acknowledgements
We thank K. Basler, H. Nakato, S. Eaton, N. Perrimon, T. Kornberg, W. Gehring, J.P. Vincent, O. Shimmi and the Bloomington Stock Centre for fly lines, E. Laufer and T. Jessell for the pMad antibody and F. Bonath for technical assistance. We are indebted to B. Müller and K. Basler for sharing unpublished data at initial stages of the project. We are grateful to W. Driever, B. Hartmann, F. Hamaratoglou and M. Simons for comments on the manuscript, A. Weiss for suggesting the name pentagone and the Life Imaging Facility of SFB592 for technical support. Work in the laboratory of M.A. was supported by the Kantons Basel-Stadt and Basel-Land, by the Swiss National Science Foundation and by SystemsX.ch within the framework of the wingX RTD. A.S. was supported by a fellowship of Research Training Program GRK1104 and by the Spemann Graduate School of Biology and Medicine. Research in the G.P. laboratory was funded by a grant of the DFG collaborative research centre SFB592.
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R.V., A.S., S.K. and G.P. performed and analysed experiments. L.P. and M.H. contributed the zebrafish experiments. R.V., M.H., M.A. and G.P. designed and supervised experiments. G.P. wrote the manuscript.
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Vuilleumier, R., Springhorn, A., Patterson, L. et al. Control of Dpp morphogen signalling by a secreted feedback regulator. Nat Cell Biol 12, 611–617 (2010). https://doi.org/10.1038/ncb2064
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DOI: https://doi.org/10.1038/ncb2064
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