Crossveinless d is a vitellogenin - like lipoprotein that binds BMPs and HSPGs , and is required for normal BMP signaling in the Drosophila wing

INTRODUCTION The localized BMP signaling that initiates the development of the posterior cross vein (PCV) from the epithelia of the Drosophila melanogaster pupal wing depends in large part on the BMPs Decapentaplegic (Dpp) and Glass bottom boat (Gbb), which are secreted from the earlier arising longitudinal veins (LVs) (Conley et al., 2000; Ray and Wharton, 2001; Ralston and Blair, 2005). Although it is not known why signaling is heightened specifically in the PCV region, the sensitivity of PCV development to reductions in the range or levels of BMP signaling has allowed the isolation and characterization of several regulators of BMP signaling. Loss of the secreted BMP-binding proteins Short gastrulation (Sog), Crossveinless-Twisted gastrulation 2 (Cv-Tsg2), Tolloid-related (Tlr; Tok – FlyBase) or Crossveinless 2 (Cv-2, also known as BMPER in vertebrates) reduces BMP signaling in the developing PCV: Sog and Cv-Tsg2 are thought to increase the movement of BMPs from the LVs to the PCV, Tlr to release BMPs from Sog, and Cv-2 to increase the transfer of BMPs to their receptors (Conley et al., 2000; Serpe et al., 2005; Shimmi et al., 2005a; Vilmos et al., 2005; Serpe et al., 2008). The LVs are less sensitive to these factors largely because they are specified much earlier in development by other pathways. We here use the sensitivity of the PCV to identify and characterize the gene mutated by crossveinless d (cv-d), first isolated by Bridges (Bridges, 1935). We found the cv-d encodes a vitellogenin-like lipoprotein, similar to the vitellogenins that comprise the major constituents of yolk in animal embryos. Cv-d binds BMPs and heparan sulfate proteoglycans (HSPGs) and increases BMP signaling in the PCV, probably by increasing the range of BMP signaling.