Morphogens are signaling molecules that can be distributed in a developing tissue along a concentration Eprazinone dihydrochloride gradient and affect development in a concentration-dependent manner. The formation and interpretation of the gradient are BMS-911543 regulated at multiple levels. The Drosophila morphogen Wingless is one of the founding members of the Wnt family of signaling molecules. In Drosophila embryo and imaginal disc development, Wg has been shown to act as a long-range morphogen. In the best-studied wing disc, Wg is expressed in several rows of cells at the dorsoventral boundary in the prospective wing pouch region. Wg can be secreted from producing cells or localized extracellularly to form a concentration gradient to regulate target genes at different levels. Although Wg is secreted from the apical surface of its producing cells, extracellular Wg is localized primarily on the basolateral surface. ExWg can be detected within a few rows of cells away from its producing cells at the Ap surface but spreads more than 20 cells away at the lateral surface. These results suggest that the longrange movement of exWg occurs on the Ba surface. However, the mechanisms by which exWg moves short distances along the Ap surface and longer distances along the Ba surface remain unclear. In receiving cells, Wg can also be found in puncta representing internalized Wg. The internalization of Wg is dependent on endocytosis and occurs at both Ap and Ba surfaces. Whereas the secretion and degradation of Wg are dependent on dynamin, the movement or distribution of exWg is independent of endocytosis. Wg distribution is affected by heparan sulfate proteoglycans, which are proteins modified by heparan sulfate glycosaminoglycan chain attachments. Enzymes for GAG and HS synthesis, such as Sulfateless and Brother of tout-velu, are required for exWg distribution. These results suggest that the exWg movement requires HSPGs. Within large sfl and botv mutant clones, although exWg is reduced, there is Wg accumulation within and behind the clone, suggesting that some HSPG from neighboring wild-type cells can act nonautonomously. Because the two HSPGs known to affect Wg signaling, Dally and Dally-like, are membrane-anchored, an unidentified diffusible HSPG is predicted to serve this role.