The long-range activity of Hedgehog is regulated in the apical extracellular space by the glypican Dally and the hydrolase Notum

Dev Cell. 2010 Apr 20;18(4):605-20. doi: 10.1016/j.devcel.2010.02.015.


Cell fate determination during developmental patterning is often controlled by concentration gradients of morphogens. In the epithelial field, morphogens like the Hedgehog (Hh) peptides diffuse both apically and basolaterally; however, whether both pools of Hh are sensed at the cellular level is unclear. Here, we show that interfering with the amount of apical Hh causes a dramatic change in the long-range activation of low-threshold Hh target genes, without similar effect on short-range, high-threshold targets. We provide genetic evidence that the glypican Dally upregulates apical Hh levels, and that the release of Dally by the hydrolase Notum promotes apical Hh long-range activity. Our data suggest that several pools of Hh are perceived in epithelial tissues. Thus, we propose that the overall gradient of Hh is a composite of pools secreted by different routes (apical and basolateral), and that a cellular summation of these components is required for appropriate developmental patterning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Body Patterning
  • Cell Lineage
  • Crosses, Genetic
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Endocytosis
  • Gene Expression Regulation, Developmental
  • Green Fluorescent Proteins / metabolism
  • Hedgehog Proteins / metabolism*
  • Membrane Glycoproteins / metabolism*
  • Microscopy, Fluorescence / methods
  • Models, Biological
  • Proteoglycans / metabolism*
  • Signal Transduction


  • Drosophila Proteins
  • Hedgehog Proteins
  • Membrane Glycoproteins
  • Notum protein, Drosophila
  • Proteoglycans
  • dally protein, Drosophila
  • Green Fluorescent Proteins