Abstract
Morphogens are signaling molecules that regulate growth and patterning during development by forming a gradient and activating different target genes at different concentrations. The extracellular distribution of morphogens is tightly regulated, with the Drosophila morphogen Wingless (Wg) relying on Dally-like (Dlp) and transcytosis for its distribution. However, in the absence of Dlp or endocytic activity, Wg can still move across cells along the apical (Ap) surface. We identified a novel secreted heparan sulfate proteoglycan (HSPG) that binds to Wg and promotes its extracellular distribution by increasing Wg mobility, which was thus named Carrier of Wg (Cow). Cow promotes the Ap transport of Wg, independent of Dlp and endocytosis, and this function addresses a previous gap in the understanding of Wg movement. This is the first example of a diffusible HSPG acting as a carrier to promote the extracellular movement of a morphogen.
Highlights
Morphogens are signaling molecules that can be distributed in a developing tissue along a concentration gradient and affect development in a concentration-dependent manner
We showed that Carrier of Wg (Cow) is a secreted heparan sulfate proteoglycan (HSPG) that can physically interact with Wg (Figure 4)
The binding to Wg is dependent on the heparan sulfate (HS) modification on Cow, and it can occur after both proteins are secreted (Figure 4)
Summary
Morphogens are signaling molecules that can be distributed in a developing tissue along a concentration gradient and affect development in a concentration-dependent manner. Wg can be secreted from producing cells or localized extracellularly to form a concentration gradient to regulate target genes at different levels [5], [6]. Wg is secreted from the apical (Ap) surface of its producing cells [7], [8], extracellular Wg (exWg) is localized primarily on the basolateral (Ba) surface [5]. 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 [7]. These results suggest that the longrange movement of exWg occurs on the Ba surface. The mechanisms by which exWg moves short distances along the Ap surface and longer distances along the Ba surface remain unclear
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