Crossveinless 2 contains cysteine-rich domains and is required for high levels of BMP-like activity during the formation of the cross veins in Drosophila

The BMP-like signaling mediated by the ligands Dpp and Gbb is required to r einforce the development of most veins in the Drosophila wing. However, the formation of the cross veins is especially sensitive to reductions in BMP- like signaling. We show here that the formation of the definitive cross vei ns occurs after the initial specification of the longitudinal veins in a pr ocess that requires localized BMP-like activity. Since Dpp and Gbb levels a re not detectably higher in the early phases of cross vein development, oth er factors apparently account for this localized activity. Our evidence sug gests that the product of the crossveinless 2 gene is a novel member of the BMP-like signaling pathway required to potentiate Gbb of Dpp signaling in the cross veins. crossveinless 2 is expressed at higher levels in the devel oping cross veins and is necessary for local BMP-like activity. The Crossve inless 2 protein contains a putative signal or transmembrane sequence, and a partial Von Willebrand Factor D domain similar to those known to regulate the formation of intramolecular and intermolecular bonds. It also contains five cysteine-rich domains, similar to the cysteine-rich domains found in Chordin, Short Gastrulation and Procollagen that are known to bind BMP-like ligands. These features strongly suggest that Crossveinless 2 acts extrace lluarly or in the secretory pathway to directly potentiate Dpp or Gbb signa ling.