Holy Tolloido: Tolloid cleaves SOG/Chordin to free DPP/BMPs

The molecular mechanism by which a group of zygotically acting genes identified almost 15 years ago[1]establishes dorsal cell fates in Drosophila is just being elucidated. A similar mechanism has been found in the establishment of the dorsal–ventral axis in the vertebrate embryo. The key genes in these processes are TGF-β molecules, Decapentaplegic (DPP) in flies and bone morphogenetic proteins (BMPs) in vertebrates. Conservation of genes in the DPP/BMP pathway in vertebrates and invertebrates strongly indicates that the basic mechanism establishing dorsal–ventral pattern formation has been conserved throughout evolution. Although both sets of genes establish non-neural ectodermal derivatives, the axes from which these cell types originate have opposite designations to each other: ventral in vertebrates is dorsal in invertebrates, and vice versa[2]. Here I discuss the mechanism recently identified by which the metalloprotease Tolloid in flies, frogs and zebrafish functions in a double inhibition mechanism to establish the graded activity of DPP/BMPs along the dorsal–ventral axis. To place the role of tolloid/Xolloid into context, I first review data on the function of other genes in the pathway.