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The cell-surface proteoglycan Dally regulates Wingless signalling in Drosophila

Abstract

Wingless (Wg) is a member of the Wnt family of growth factors, secreted proteins that control proliferation and differentiation during development. Studies in Drosophila have shown that responses to Wg require cell-surface heparan sulphate, a glycosaminoglycan component of proteoglycans1,2,3,4. These findings suggest that a cell-surface proteoglycan is a component of a Wg/Wnt receptor complex. We demonstrate here that the protein encoded by the division abnormally delayed (dally) gene is a cell-surface, heparan-sulphate-modified proteoglycan5,6. dally partial loss-of-function mutations compromise Wg-directed events, and disruption of dally function with RNA interference produces phenotypes comparable to those found with RNA interference of wg or frizzled (fz)/Dfz2 (ref. 7). Ectopic expression of Dally potentiates Wg signalling without altering levels of Wg and can rescue a wg partial loss-of-function mutant. We also show that dally, a regulator of Decapentaplegic (Dpp) signalling during post-embryonic development, has tissue-specific effects on Wg and Dpp signalling. Dally can therefore differentially influence signalling mediated by two growth factors, and may form a regulatory component of both Wg and Dpp receptor complexes.

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Figure 1: Biochemical characterization of HA-Dally.
Figure 2: dally affects cuticle patterning in the embryo.
Figure 3: Effects of ectopic Dally expression on cellular responses to Wg.
Figure 4: Rescue of wg partial loss-of-function mutants by ectopic dally + expression and expression patterns of dally +.
Figure 5: Selective participation of dally in Dpp signalling during genitalia development.

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Acknowledgements

We thank S. Cumberledge, E. Wieschaus and S. Carroll for antibodies; X. Lin, N.Perrimon and A. Manoukian for providing sgl alleles; A. Lander for providing critical assistance with proteoglycan biochemistry; K. Kamdar for contributions to the RNAi experiments; M. Pankonin for assistance with genetic experiments; and D. Brower for his critical reading of the manuscript. Work in the laboratory of H.N. was supported by a grant-in-Aid for Scientific Research and the Kanagawa Academy of Science and Technology; work in the laboratory of S.B.S. was funded by a grant from the March of Dimes, and by NIH salary support for W. Staatz and M. Humphrey; B. Fox is supported by an NIH award to Arthur Lander; S.B.S. is a fellow of the Alfred P. Sloane Foundation.

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Correspondence to Scott B. Selleck.

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Tsuda, M., Kamimura, K., Nakato, H. et al. The cell-surface proteoglycan Dally regulates Wingless signalling in Drosophila. Nature 400, 276–280 (1999). https://doi.org/10.1038/22336

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