The roles of the cysteine rich domain proteins Crossveinless 2, Short gastrulation, and Twisted gastrulation 2 during crossvein patterning in the wing of Drosophila melanogaster

The adult wing of the fruit fly Drosophila melanogaster contains a system of interconnected longitudinal veins and crossveins that are important for flight. Wing veins do not develop by invasion, but differentiate from the wing epithelium in response to the localized activation of highly conserved signaling pathways. The longitudinal veins are therefore an important model for understanding the genetic basis of the development of adult form. The crossveins present a unique set of developmental patterning problems, yet little is known about the molecular mechanisms by which the crossveins are positioned. Here I present evidence that signaling by the Bone Morphogenetic Protein (BMP) pathway plays an unusual role during the development of the crossveins, and especially the posterior crossvein (PCV), and provides a molecular mechanism by which the development of the PCV and the longitudinal veins can be spatially coordinated. Three genes, crossveinless 2 ( cv-2), short gastrulation (sog), and twisted gastrulation 2 (tsg 2) are important for crossvein development and encode members of the growing family of Cysteine Rich (CR) domain proteins that participate in BMP signaling during vertebrate and invertebrate development. I present evidence that the highly conserved proteins Cv-2, Sog, and Tsg 2 are essential for BMP signaling in the developing crossveins. My data are consistent with a model in which Sog and Tsg 2 form a complex with BMP ligands to promote their long-range transport or signaling within a crossvein competent zone, a region that is uniquely sensitive to BMP signals. This signaling is enhanced by Cv-2, a novel CR domain protein whose activity is regulated by cleavage at a highly conserved site. Finally, I discuss other factors that may participate in defining the crossvein competent zones or in modulating BMP signaling in these regions.