Drosophila glypicans Dally and Dally-like are essential regulators for JAK/STAT signaling and Unpaired distribution in eye development

Dev Biol. 2013 Mar 1;375(1):23-32. doi: 10.1016/j.ydbio.2012.12.019. Epub 2013 Jan 8.

Abstract

The highly conserved janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is a well-known signaling system that is involved in many biological processes. In Drosophila, this signaling cascade is activated by ligands of the Unpaired (Upd) family. Therefore, the regulation of Upd distribution is one of the key issues in controlling the JAK/STAT signaling activity and function. Heparan sulfate proteoglycans (HSPGs) are macromolecules that regulate the distribution of many ligand proteins including Wingless, Hedgehog and Decapentaplegic (Dpp). Here we show that during Drosophila eye development, HSPGs are also required in normal Upd distribution and JAK/STAT signaling activity. Loss of HSPG biosynthesis enzyme Brother of tout-velu (Botv), Sulfateless (Sfl), or glypicans Division abnormally delayed (Dally) and Dally-like protein (Dlp) led to reduced levels of extracellular Upd and reduction in JAK/STAT signaling activity. Overexpression of dally resulted in the accumulation of Upd and up-regulation of the signaling activity. Luciferase assay also showed that Dally promotes JAK/STAT signaling activity, and is dependent on its heparin sulfate chains. These data suggest that Dally and Dlp are essential for Upd distribution and JAK/STAT signaling activity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Drosophila / genetics
  • Drosophila / growth & development
  • Drosophila / metabolism*
  • Drosophila Proteins / biosynthesis
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Eye / growth & development
  • Eye / metabolism
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Developmental
  • Heparan Sulfate Proteoglycans / metabolism
  • Imaginal Discs / metabolism*
  • Janus Kinases / genetics
  • Janus Kinases / metabolism*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • N-Acetylglucosaminyltransferases / biosynthesis
  • N-Acetylglucosaminyltransferases / genetics
  • Proteoglycans / genetics
  • Proteoglycans / metabolism*
  • RNA Interference
  • RNA, Small Interfering
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / metabolism*
  • Signal Transduction
  • Sulfotransferases / biosynthesis
  • Sulfotransferases / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Drosophila Proteins
  • Heparan Sulfate Proteoglycans
  • Membrane Glycoproteins
  • Proteoglycans
  • RNA, Small Interfering
  • STAT Transcription Factors
  • Transcription Factors
  • dally protein, Drosophila
  • dlp protein, Drosophila
  • upd1 protein, Drosophila
  • Botv protein, Drosophila
  • N-Acetylglucosaminyltransferases
  • Janus Kinases
  • hop protein, Drosophila
  • Sulfotransferases
  • sfl protein, Drosophila