title: The long-range activity of Hedgehog is regulated in the apical extracellular space by the glypican Dally and the hydrolase Notum.
abstract: 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.
authors.affiliation: Institut Biologie du Développement & Cancer-IBDC, Université de Nice Sophia-Antipolis, UMR6543 CNRS, Centre de Biochimie, Parc Valrose, 06108 Nice Cedex 2, France.
authors.forename: Katie L
authors.initials: KL
authors.lastname: Ayers
authors.forename: Armel
authors.initials: A
authors.lastname: Gallet
authors.forename: Laurence
authors.initials: L
authors.lastname: Staccini-Lavenant
authors.forename: Pascal P
authors.initials: PP
authors.lastname: Thérond
mesh_terms: D000483:Alleles; D000818:Animals; D019521:Body Patterning; D019070:Cell Lineage; D003433:Crosses, Genetic; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D004705:Endocytosis; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence / Q000379:methods; D008954:Models, Biological; D011509:Proteoglycans / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D008562:Membrane Glycoproteins; C456459:Notum protein, Drosophila; D011509:Proteoglycans; C098128:dally protein, Drosophila; D049452:Green Fluorescent Proteins