Signaling from the Right Place

Science Signaling  09 Sep 2008:
Vol. 1, Issue 36, pp. ec318
DOI: 10.1126/scisignal.136ec318

During embryonic development, gradients of secreted morphogens provide cues to target cells, thereby playing a critical role in tissue patterning. Noting that, in the absence of a protein complex, diffusion of the bone morphogenetic protein (BMP) Decapentaplegic (Dpp) in the Drosophila embryo is limited, Wang et al. investigated the role of the extracellular matrix in Dpp signaling. Biologically active Dpp bound to the C termini of the type IV collagens Viking (Vkg) and DCg1, as did heterodimers of Dpp and the BMP Screw (Dpp-Scw); mutational analysis of Vkg identified a Dpp-binding sequence that was conserved in mosquito, worm, mouse, and human type IV collagens. Vkg was present in Drosophila embryos at the time the Dpp gradient arises and also in the germarium of the ovary (where Dpp secreted from nearby somatic niche cells inhibits germline stem cells from differentiating). The phenotypes of embryos expressing reduced amounts of Vkg or DCg1 resembled those of embryos with reduced Dpp; moreover, Dpp was found in a narrower protein domain. In contrast, Vkg overexpression expanded the area in which the Dpp target gene Race was expressed. In germaria of flies lacking Vkg, however, there were more germline stem cells, a phenotype consistent with Dpp overexpression. Addition of the two BMP-binding proteins Short gastrulation and Twisted gastrulation (required for formation of the Dpp-Scw gradient in early embryos) released Dpp-Scw from a glutathione S-transferase-Vkg C-terminal tail fusion protein. Conversely, the Vkg C terminus promoted interaction of Dpp-Scw with a BMP receptor. The authors conclude that type IV collagens regulate Dpp signaling, promoting gradient formation in the embryo and restricting Dpp localization (and thereby its signaling range) in the germarium.

X. Wang, R. E. Harris, L. J. Bayston, H. L. Ashe, Type IV collagens regulate BMP signalling in Drosophila. Nature 455, 72-77 (2008). [PubMed]