Glypicans, a family of heparan sulfate proteoglycans attached to the cell surface via a glycosylphosphatidylinositol (GPI)-anchor, play essential roles in morphogen signaling and distributions. A Drosophila glypican, Dally, regulates the gradient formation of Decapentaplegic (Dpp) in the developing wing. To gain insights into the function of glypicans in morphogen signaling, we examined the activities of two mutant forms of Dally: a transmembrane form (TM-Dally) and a secreted form (Sec-Dally). Misexpression of tm-dally in the wing disc had a similar yet weaker effect in enhancing Dpp signaling compared to that of wild-type dally. In contrast, Sec-Dally shows a weak dominant negative activity on Dpp signal transduction. Furthermore, sec-dally expression led to patterning defects as well as a substantial overgrowth of tissues and animals through the expansion of the action range of Hh. These findings support the recently proposed model that secreted glypicans have opposing and/or distinct effects on morphogen signaling from the membrane-tethered forms.
Bibliographical noteFunding Information:
We are grateful to T. Tabata, P. ten Dijke, D. Duncan, R. Holmgren, I. Guerrero, R. Ueda, T. Neufeld and the Bloomington Stock Center for fly stocks and reagents. We acknowledge the contribution of M. Sugiura in the construction of dally mutant forms. We thank C. Kirkpatrick and A. Swearingen for critical reading of the manuscript and helpful comments. This work was supported by research grants from NIH (R01 HD042769) and Human Frontier Science Program.
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- Heparan sulfate proteoglycan