Regulation of morphogen pathways by a Drosophila chondroitin sulfate proteoglycan Windpipe

J Cell Sci. 2023 Apr 1;136(7):jcs260525. doi: 10.1242/jcs.260525. Epub 2023 Apr 11.


Morphogens provide quantitative and robust signaling systems to achieve stereotypic patterning and morphogenesis. Heparan sulfate (HS) proteoglycans (HSPGs) are key components of such regulatory feedback networks. In Drosophila, HSPGs serve as co-receptors for a number of morphogens, including Hedgehog (Hh), Wingless (Wg), Decapentaplegic (Dpp) and Unpaired (Upd, or Upd1). Recently, Windpipe (Wdp), a chondroitin sulfate (CS) proteoglycan (CSPG), was found to negatively regulate Upd and Hh signaling. However, the roles of Wdp, and CSPGs in general, in morphogen signaling networks are poorly understood. We found that Wdp is a major CSPG with 4-O-sulfated CS in Drosophila. Overexpression of wdp modulates Dpp and Wg signaling, showing that it is a general regulator of HS-dependent pathways. Although wdp mutant phenotypes are mild in the presence of morphogen signaling buffering systems, this mutant in the absence of Sulf1 or Dally, molecular hubs of the feedback networks, produces high levels of synthetic lethality and various severe morphological phenotypes. Our study indicates a close functional relationship between HS and CS, and identifies the CSPG Wdp as a novel component in morphogen feedback pathways.

Keywords: Drosophila; Chondroitin sulfate proteoglycan; Decapentaplegic; Morphogen signaling; Windpipe; Wingless.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chondroitin Sulfate Proteoglycans / genetics
  • Chondroitin Sulfate Proteoglycans / metabolism
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Drosophila* / metabolism
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism
  • Heparan Sulfate Proteoglycans / genetics
  • Heparan Sulfate Proteoglycans / metabolism
  • Sulfatases / genetics
  • Sulfatases / metabolism
  • Wnt1 Protein / genetics
  • Wnt1 Protein / metabolism


  • Chondroitin Sulfate Proteoglycans
  • dpp protein, Drosophila
  • Drosophila Proteins
  • Hedgehog Proteins
  • Heparan Sulfate Proteoglycans
  • SULF1 protein, Drosophila
  • Sulfatases
  • Wnt1 Protein
  • wdp protein, Drosophila