Structure and functional analysis of Shrew, a novel modulator of the BMP signalling pathway

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor (TGF)"B"family of signalling molecules and are essential for embryonic development and tissue homeostasis. BMP signalling is highly conserved from flies to humans and plays an important role at multiple developmental stages, including patterning of the embryonic dorsal-ventral (DV) axis and during bone formation. This conservation means that powerful model organisms such as Drosophila can be utilised to visualise signalling in vivo. BMP (called Dpp in Drosophila) signalling is controlled by a group of proteins which form inhibitory complexes with Dpp. One such regulator, Sog acts by binding to Dpp thereby physically preventing their association with receptors on the cell surface. Sog is assisted by a modulator, twisted gastrulation, which can have both pro- and anti-Dpp functions. Recently, a new member of this signalling pathway was discovered, Shrew, a novel twisted gastrulation-like protein that functions to regulate DV patterning in Drosophila by increasing Dpp activity, although its mechanism of action is unknown.