Expression of a secreted form of Dally, a Drosophila glypican, induces overgrowth phenotype by affecting action range of Hedgehog

Satomi Takeo, Takuya Akiyama, Cyndy Firkus, Toshiro Aigaki, Hiroshi Nakato

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)204-218
Number of pages15
JournalDevelopmental Biology
Volume284
Issue number1
DOIs
StatePublished - Aug 1 2005

Bibliographical note

Funding 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.

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

Keywords

  • Decapentaplegic
  • Drosophila
  • GPI-anchor
  • Glypican
  • Hedgehog
  • Heparan sulfate proteoglycan
  • Morphogen
  • dally

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