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Dally cooperates with Drosophila Frizzled 2 to transduce Wingless signalling

Abstract

The Drosophila wingless gene (wg) encodes a protein of the Wnt family and is a critical regulator in many developmental processes1. Biochemical studies have indicated that heparan sulphate proteoglycans, consisting of a protein core to which heparan sulphate glycosaminoglycans are attached2, are important for Wg function3. Here we show that, consistent with these findings, the Drosophila gene sulfateless (sfl), which encodes a homologue of vertebrate heparan sulphate N -deacetylase/N -sulphotransferase (an enzyme needed for the modification of heparan sulphate) is essential for Wg signalling. We have identified the product of division abnormally delayed (dally), a glycosyl-phosphatidyl inositol (GPI)-linked glypican, as a heparan sulphate proteoglycan molecule involved in Wg signalling. Our results indicate that Dally may act as a co-receptor for Wg, and that Dally, together with Drosophila Frizzled 2, modulates both short- and long-range activities of Wg.

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Figure 1: sfl is required for Wg signalling.
Figure 2: sfl encodes heparan sulphate N -deacetylase/N -sulphotransferase (NDST).
Figure 3: dally is a segment-polarity gene.
Figure 4: Heparan sulphate GAG modification of Dally in sfl mutants.
Figure 5: Dally is required for Wg/DFz2 signalling in wing patterning.

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Acknowledgements

We thank R. Carthew, I. Duncan, H. Nakato, R. Nusse, M. Peifer and S. Selleck for reagents; S. Selleck and S. Kerridge for exchange of information before publication; and E. Bach, D. Bilder, U. Haecker, K. Hong, A. Michelson, B. Mathey-Prevot and I. The for comments on the manuscript. This work is supported by the US Army Medical Research and Material Command (X.L.) and HHMI (N.P.).

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Lin, X., Perrimon, N. Dally cooperates with Drosophila Frizzled 2 to transduce Wingless signalling. Nature 400, 281–284 (1999). https://doi.org/10.1038/22343

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