The Cell-Surface Proteoglycan Dally Regulates Wingless Signalling in Drosophila

Nature. 1999 Jul 15;400(6741):276-80. doi: 10.1038/22336.

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 proteoglycans. 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 proteoglycan. 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. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cloning, Molecular
  • Drosophila / genetics
  • Drosophila / physiology*
  • Drosophila Proteins*
  • Epidermis / embryology
  • Epidermis / physiology
  • Female
  • Genes, Insect
  • Genetic Techniques
  • Genitalia / embryology
  • Glycosylphosphatidylinositols / chemistry
  • Glycosylphosphatidylinositols / physiology
  • Heparan Sulfate Proteoglycans / chemistry
  • Heparan Sulfate Proteoglycans / physiology
  • Homeodomain Proteins / physiology
  • Insect Proteins / physiology
  • Larva / chemistry
  • Male
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Mutation
  • Proteoglycans / chemistry
  • Proteoglycans / genetics
  • Proteoglycans / physiology*
  • Proto-Oncogene Proteins / physiology*
  • RNA / metabolism
  • Signal Transduction*
  • Transcription Factors / physiology
  • Wnt1 Protein

Substances

  • Drosophila Proteins
  • En protein, Drosophila
  • Glycosylphosphatidylinositols
  • Heparan Sulfate Proteoglycans
  • Homeodomain Proteins
  • Insect Proteins
  • Membrane Glycoproteins
  • Proteoglycans
  • Proto-Oncogene Proteins
  • Transcription Factors
  • Wnt1 Protein
  • dally protein, Drosophila
  • dpp protein, Drosophila
  • wg protein, Drosophila
  • RNA