Drosophila homolog of vertebrate Bmp2/Bmp4, and the Bmp- binding protein Short gastrulation (Sog), the homolog of vertebrate chordin, function antagonistically to ensure the formation of straight continuous veins

Vein differentiation is controlled by groups of genes that act in two developmentally distinct phases. During mid-third larval instar and early prepupal stages, the positions of vein territories are defined within the monolayer of wing imaginal disc cells (reviewed by Bier, 2000). In the second phase of vein development, during pupal stages, the vein versus intervein cell fate choice is resolved among cells in broad vein competent domains of a bilayered wing primordium. This refinement step is mediated in part by lateral inhibitory signals elaborated by presumptive vein cells. At the same time that lateral inhibition limits the width of veins, vein continuity signals act along the axis of the vein to promote their formation in straight continuous lines. Genes such as net (Brentrup et al., 2000) and blistered (Roch et al., 1998), which govern intervein development, are also required for restricting vein development to appropriate cells. In addition, the activity of intervein genes, which are required for intersurface adhesion, such as those coding for the integrins, must be excluded from veins to permit the nonadherent strips of cells in the veins to form open channels between the two wing surfaces (Brown, 2000). Interestingly, some combinations of integrin mutants have been found to generate ectopic veins; however, the mechanisms that underlie this phenotype are not understood (Brower and Jaffe, 1989; Brown et al., 1989; Zusman et al., 1993; Zusman et al., 1990). During early pupal development, Decapentaplegic (Dpp), the Drosophila homolog of vertebrate Bmp2/Bmp4, and the Bmpbinding protein Short gastrulation (Sog), the homolog of vertebrate chordin, function antagonistically to ensure the formation of straight continuous veins (Haerry et al., 1998; Lecuit et al., 1996; Sturtevant and Bier, 1995; Yu et al., 1996; Zecca et al., 1995). Throughout this period, dpp is expressed in vein primordia, while sog is expressed in a complementary intervein pattern (Yu et al., 1996). Sog also opposes Bmp signaling during dorsoventral patterning of the early embryo, which involves zygotic (Biehs et al., 1996; Francois et al., 1994; Marques et al., 1997) as well as maternal (Araujo and Bier, 2000) functions of this pathway. sog encodes a secreted molecule with domains resembling thrombospondin and procollagen (Francois and Bier, 1995; Francois et al., 1994) and has been shown to bind Dpp (Ross et al., 2001). It has been suggested that regulated cleavage of Sog generates different forms with distinct activities (Yu et al., 2000). Cleavage at three sites by the metalloprotease Tolloid (Tld) inactivates Sog (Marques et al., 1997), while alternative cleavage at a different site, which occurs in the presence of the co-factor Twisted Gastrulation (Tsg), results in the production of truncated forms of Sog referred to as Supersog, which antagonize a broader spectrum of Bmp activities than intact Sog (Yu et al., 2000). Chordin is also subject to proteolysis by Xolloid, the vertebrate homolog of Tolloid (Piccolo et al., 1997). Because all of these molecules interact extracellularly, it 3851 Development 130, 3851-3864 © 2003 The Company of Biologists Ltd doi:10.1242/dev.00613