Type IV collagens regulate BMP signalling in Drosophila

• Published in: Nature Vol. 455; no. 7209; pp. 72 - 77
• Main Authors: Wang, Xiaomeng, Harris, Robin E., Bayston, Laura J., Ashe, Hilary L.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.09.2008; Nature Publishing; Nature Publishing Group
• Subjects: Amino acids; Animals; Biological and medical sciences; Body Patterning; Bone morphogenetic proteins; Bone Morphogenetic Proteins - genetics; Bone Morphogenetic Proteins - metabolism; Cell Count; Cells; Collagen; Collagen Type IV - genetics; Collagen Type IV - metabolism; Drosophila; Drosophila melanogaster - embryology; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; E coli; Embryology: invertebrates and vertebrates. Teratology; Embryos; Female; Fundamental and applied biological sciences. Psychology; Humanities and Social Sciences; Insects; Male; Methods; Molecular embryology; multidisciplinary; Ovary - cytology; Ovary - metabolism; Physiological aspects; Protein Binding; Proteins; Science; Science (multidisciplinary); Signal Transduction; Signals and signaling; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; Vertebrates; Embryonic development; Insecta; Drosophila; Dorsoventral axis; Protein; Drosophilidae; Morphogenesis; Molecular signal; Arthropoda; Collagen; Extracellular matrix; Invertebrata; Diptera
• ISSN: 0028-0836; 1476-4687; 1476-4687; 1476-4679
• DOI: 10.1038/nature07214

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. Dorsal–ventral patterning: collagens and BMP signalling In both vertebrate and invertebrate embryos dorsal-ventral patterning is controlled by a concentration gradient of secreted signalling molecules called BMPs or bone morphogenetic proteins. Work in Drosophila now shows the extracellular matrix pays a part in regulating the Dpp morphogen gradient (Dpp is the Drosophila form of BMP). Type IV collagen binds to the Dpp ligand and regulates its signalling in the Drosophila embryo and ovary by sequestering Dpp. Human type IV collagen binds the analogous protein in humans, BMP-4, suggesting that this role of type IV collagens is widely conserved. This paper establishes a role of the extracellular matrix for regulating the BMP morphogen gradient responsible for dorsal–ventral patterning of vertebrate and invertebrate embryos. Type IV collagen binds to the Dpp ligand (the Drosophila form of BMP) and regulates its signalling in the Drosophila embryo and ovary by sequestering Dpp. Human type IV collagen binds the analogous protein in humans.