In many developmental contexts, a locally produced morphogen specifies positional information by forming a concentration gradient over a field of cells1. However, during embryonic dorsal–ventral patterning in Drosophila, two members of the bone morphogenetic protein (BMP) family, Decapentaplegic (Dpp) and Screw (Scw), are broadly transcribed but promote receptor-mediated signalling in a restricted subset of expressing cells2,3,4. Here we use a novel immunostaining protocol to visualize receptor-bound BMPs and show that both proteins become localized to a sharp stripe of dorsal cells. We demonstrate that proper BMP localization involves two distinct processes. First, Dpp undergoes directed, long-range extracellular transport. Scw also undergoes long-range movement, but can do so independently of Dpp transport. Second, an intracellular positive feedback circuit promotes future ligand binding as a function of previous signalling strength. These data elicit a model in which extracellular Dpp transport initially creates a shallow gradient of BMP binding that is acted on by positive intracellular feedback to produce two stable states of BMP–receptor interactions, a spatial bistability in which BMP binding and signalling capabilities are high in dorsal-most cells and low in lateral cells.
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We thank N. Dostatni, M. Levine and M. Markstein for fly stocks; S. Cohen, M. Levine and M. Markstein for plasmids; P. ten Dijke and C. Heldin for antibodies; V. Bindokas for assistance with confocal microscopy; S. Lemke and M. Markstein for discussions; D. Bishop, M. O. Casanueva, C. Li, A. Mahowald, J. Malamy, M. Markstein, V. Prince and J. Staley for helpful comments on the manuscript, and M. O'Connor for sharing unpublished data and reagents. Preliminary data on the second function of Tsg were obtained by E. Decotto. Funding was provided by grants to E.L.F. from the NIH and from the Human Frontiers Science program.
The authors declare that they have no competing financial interests.
This figure shows that there is a limited amount of Dpp diffusion in the absence of Sog. (DOC 1126 kb)
This figure shows that Tsg promotes BMP signalling independent of Sog (DOC 1459 kb)
This figure presents a characterization of sog; scw mutant embryos. (DOC 771 kb)
This figure shows the relationship between tld and sog expression patterns and BMP signaling. (DOC 1209 kb)
This figure shows that the pattern of tld expression is not affected before the onset of gastrulation in a dpp null embryo. (DOC 668 kb)
This document contains additional details of the crosses that were performed to generate certain embryonic genotypes and additional information concerning the concentration of different primary and secondary antibodies used in these experiments. (DOC 50 kb)
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Wang, YC., Ferguson, E. Spatial bistability of Dpp–receptor interactions during Drosophila dorsal–ventral patterning. Nature 434, 229–234 (2005). https://doi.org/10.1038/nature03318
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