It plays only a minor role that is partially redundant with Dlp

Dally and Dlp belong to the glypican family of HSPGs, and both can bind to Wg and are involved in regulating Wg distribution and signaling. The movement of Wg from the Ap to Ba surface was reported to be dependent on Dlp through transcytosis, although this finding was contradicted by another study. Moreover, this vertical intracellular translocation of Wg does not explain the lateral intercellular spread of exWg. It has been proposed that Wg bound to Dlp can be transferred to adjacent Wg receptors, depending on the ratio of Dlp to DFz2, although whether this mechanism transfers Wg to adjacent cells has not yet been demonstrated. Extracellular movement of Wg at or near producing cells likely occurs independent of membrane-anchored Dlp and DFz2, as these levels are low in the Wg-producing cells at the D-V border. Furthermore, dlp-null clones do not affect the exWg level in this region, which leaves open the question of what factor is responsible for moving Wg from its source to adjacent Dlp-expressing cells. Dally is present at high levels at the D-V border, but it plays only a minor role that is partially redundant with Dlp. Even in a dally dlp double mutant clone, exWg is detected away from the producing cells. The extracellular hydrolase Notum/Wingfull can modify Dlp to reduce its ability to bind and stabilize Wg, thereby reducing, rather than promoting, the range of Wg distribution. Therefore, some unidentified factor must be responsible for moving Wg away from its source. In this study, we identified Carrier of Wg as a novel secreted HSPG. Our results showed that Cow can bind to exWg to increase its rate of movement and stability. The Deferiprone identification of Cow answers four previously unknown aspects of Wg gradient DMOG formation. First, Cow is localized primarily at the Ap surface and is responsible for the Ap movement of Wg. Second, Cow is a diffusible HSPG, which can explain the non-autonomous rescue of Wg movement inclones defective for HS synthesis. Third, Cow is present at the D-V border and is responsible for moving Wg away from its source to interact with Dlp and receptors. Fourth, diffusible Cow can mediate the transfer of Wg to adjacent cells, a role not satisfactorily explained by membrane-anchored Dlp.

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