The cell-surface proteoglycan Dally regulates Wingless signalling in Drosophila

Wingless (Wg) is a member of the Wnt family of growth factors, secreted pro teins that control proliferation and differentiation during development. St udies in Drosophila have shown that responses to Wg require cell-surface he paran sulphate, a glycosaminoglycan component of proteoglycans(1-4). These findings suggest that a cell-surface proteoglycan is a component of a Wg/Wn t receptor complex. We demonstrate here that the protein encoded by the div ision abnormally delayed (dally) gene is a cell-surface, heparan-sulphate-m odified proteoglycan(5,6). dally partial loss-of-function mutations comprom ise Wg-directed events, and disruption of daily function with RNA interfere nce produces phenotypes comparable to those found with RNA interference of wg or frizzled (fz)/Dfz2 (ref. 7). Ectopic expression of Daily potentiates Wg signalling without altering levels of Wg and can rescue a wg partial los s-of-function mutant, We also show that dally a regulator of Decapentaplegi c (DFP) signalling during post-embryonic development, has tissue-specific e ffects on Wg and Dpp signalling. Daily can therefore differentially influen ce signalling mediated by two growth factors, and may form a regulatory com ponent of both Wg and Dpp receptor complexes.