The Role(s) of Heparan Sulfate Proteoglycan(s) in the wnt-1 Signaling Pathway

Abstract

I have identified A Drosophila gene, sulfateless (sfl) which encodes the homologue of vertebrate heparan/haparin sulfate N-deacetylase/N-sulfotransferase. This enzyme is essential for the modification and the biological activity of heparan sulfate proteoglycans (HSPG). I find that in the absence of both maternal and zygotic activities of this gene, mutant embryos develop with segment polarity phenotypes reminiscent to loss of either Wingless (Wg) or Hedgehog signaling. To analyze the function of Sfl enzymes in a specific cell-cell interaction process, I have focused my analysis on the requirement for these enzymes during Wg signaling. I report that sfl mutation impair Wg signaling during both embryonic and imaginal discs development, suggesting that HSPGs contribute to the reception of Wg. Sfl acts non cell-autonomously in Wg signaling and overexpression of Wg can bypass the requirement for this enzyme suggesting that HSPGs modulate Wg signaling, possibly by facilitating the binding of Wg to its receptor. These findings thus provide strong genetic evidence that HSPG is critical for signaling by Wg.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Aug 01, 1998
Accession Number
ADB244768

Entities

People

  • Xinhua Lin

Organizations

  • Harvard Medical School

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Animal Structures
  • Animals
  • Biology
  • Biomedical And Dental Materials
  • Cells
  • Chemistry
  • Chromosomes
  • Genes
  • Genetic Structures
  • Genetics
  • Growth Factors
  • Molecules
  • Peptides
  • Polymeric Films
  • Polysaccharides
  • Proteins

Fields of Study

  • Biology

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Molecular Biology and Genetics

Technology Areas

  • Biotechnology