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Type IV collagens regulate BMP signalling in Drosophila

Abstract

Dorsal–ventral patterning in vertebrate and invertebrate embryos is mediated by a conserved system of secreted proteins that establishes a bone morphogenetic protein (BMP) gradient. Although the Drosophila embryonic Decapentaplegic (Dpp) gradient has served as a model to understand how morphogen gradients are established, no role for the extracellular matrix has been previously described. Here we show that type IV collagen extracellular matrix proteins bind Dpp and regulate its signalling in both the Drosophila embryo and ovary. We provide evidence that the interaction between Dpp and type IV collagen augments Dpp signalling in the embryo by promoting gradient formation, yet it restricts the signalling range in the ovary through sequestration of the Dpp ligand. Together, these results identify a critical function of type IV collagens in modulating Dpp in the extracellular space during Drosophila development. On the basis of our findings that human type IV collagen binds BMP4, we predict that this role of type IV collagens will be conserved.

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Figure 1: Dpp binds to type IV collagens.
Figure 2: Type IV collagen distribution in the embryo and germarium.
Figure 3: Type IV collagens increase Dpp signalling in the embryo.
Figure 4: Collagen IV increases GSC number.
Figure 5: Mechanistic insight into the function of Dpp–collagen-IV interactions in the embryo.

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Acknowledgements

We thank M. O’Connor for plasmids, flies and advice on Dpp–HA staining; W. Chia, R. Ray and the Bloomington stock centre for fly stocks; E. Bier, P. ten Dijke, H. Bellen, L. Fessler and D. McKearin for antibodies; T. Jowitt for help with SPR; S. Lunj, M. Ronshaugen and W. Song for help; M. Ashe and W. Miles for reading the manuscript; and M. Levine whose laboratory this work was initiated in. This work was funded by a BBSRC project grant to H.L.A. and a BBSRC studentship to R.E.H.

Author Contributions H.L.A. designed and obtained funding for the experiments. X.W. generated the in vitro and embryonic data. R.E.H. performed the ovary experiments. L.J.B. provided technical assistance with cloning, fly counts and transgenics. X.W., R.E.H. and H.L.A. analysed and interpreted the data, and H.L.A. wrote the paper.

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Correspondence to Hilary L. Ashe.

Supplementary information

Supplementary Information

The file contains Supplementary Figures 1-10 with Legends and additional references The data include further characterisation of the following: collagen IV-Dpp/BMP interaction; collagen IV expression and distribution in the embryo; and phenotype of type IV collagen mutant embryos. (PDF 2500 kb)

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Wang, X., Harris, R., Bayston, L. et al. Type IV collagens regulate BMP signalling in Drosophila. Nature 455, 72–77 (2008). https://doi.org/10.1038/nature07214

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