| The Drosophila Epidermal Growth Factor Receptor (DER) is the only known erbB-like receptor in Drosophila. Signaling through DER is transduced by the highly conserved Ras/MAPK cascade. DER signaling is required at multiple stages of development for the survival, proliferation and differentiation of multiple cell types. Although DER is broadly expressed, its activity is tightly regulated by several extracellular proteins, including the activating protein, Vein (Vn).;Vn is an EGF-like protein similar to the vertebrate neuregulins and plays a critical role in both the initial development of the wing imaginal disc and in the placement and differentiation of veins in the adult wing. Hypomorphic mutations in vn cause loss of vein material, while overexpression of vn leads to the formation of ectopic veins.;I examined the role of vn in wing vein patterning by analyzing the regulation of vn expression in the third instar wing disc. In contrast to the embryo, where vn is a target of DER signaling and functions as part of a positive feedback loop, DER signaling in the wing pouch does not induce vn expression and, in fact, is capable of repressing it. Instead, vn is a target of the conserved signaling molecule Hedgehog in the wing pouch. The transcription factor Cubitus interruptus (Ci), a homolog of vertebrate Gli proteins, acts downstream of Hedgehog in this activation. Vn thus acts as a secondary signaling molecule which is instrumental in Hh-dependent patterning of the central wing.;In order to examine the relationship between vn and other genes in wing vein patterning and to potentially identify new factors involved in Vn/DER signaling, I conducted a screen to identify genes which were able to enhance or suppress an extra-vein phenotype caused by overexpression of vn. Sixty-three known genes and eight uncharacterized loci were shown to modify the extra-vein phenotype, including a putative regulator of disc growth and one which encodes a regulator of cell size. Characterization of these loci will add further to the understanding of wing vein development. |
