title: Expression of a secreted form of Dally, a Drosophila glypican, induces overgrowth phenotype by affecting action range of Hedgehog.
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.
authors.affiliation: Department of Biology, Tokyo Metropolitan University, Hachioji-shi, Tokyo 192-0397, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Takeo
authors.forename: Takuya
authors.initials: T
authors.lastname: Akiyama
authors.forename: Cyndy
authors.initials: C
authors.lastname: Firkus
authors.forename: Toshiro
authors.initials: T
authors.lastname: Aigaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakato
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D017931:DNA Primers; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D015151:Immunoblotting; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014921:Wings, Animal / Q000196:embryology*
chemical_list: D017931:DNA Primers; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C098128:dally protein, Drosophila; C064196:dpp protein, Drosophila; C077245:hh protein, Drosophila