title: Dispatched mediates Hedgehog basolateral release to form the long-range morphogenetic gradient in the Drosophila wing disk epithelium.
abstract: Hedgehog (Hh) moves from the producing cells to regulate the growth and development of distant cells in a variety of tissues. Here, we have investigated the mechanism of Hh release from the producing cells to form a morphogenetic gradient in the Drosophila wing imaginal disk epithelium. We describe that Hh reaches both apical and basolateral plasma membranes, but the apical Hh is subsequently internalized in the producing cells and routed to the basolateral surface, where Hh is released to form a long-range gradient. Functional analysis of the 12-transmembrane protein Dispatched, the glypican Dally-like (Dlp) protein, and the Ig-like and FNNIII domains of protein Interference Hh (Ihog) revealed that Dispatched could be involved in the regulation of vesicular trafficking necessary for basolateral release of Hh, Dlp, and Ihog. We also show that Dlp is needed in Hh-producing cells to allow for Hh release and that Ihog, which has been previously described as an Hh coreceptor, anchors Hh to the basolateral part of the disk epithelium.
authors.affiliation: Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Universidad Autónoma de Madrid, Cantoblanco, E-28049 Madrid, Spain.
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Callejo
authors.forename: Aphrodite
authors.initials: A
authors.lastname: Bilioni
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mollica
authors.forename: Nicole
authors.initials: N
authors.lastname: Gorfinkiel
authors.forename: Germán
authors.initials: G
authors.lastname: Andrés
authors.forename: Carmen
authors.initials: C
authors.lastname: Ibáñez
authors.forename: Carlos
authors.initials: C
authors.lastname: Torroja
authors.forename: Laura
authors.initials: L
authors.lastname: Doglio
authors.forename: Javier
authors.initials: J
authors.lastname: Sierra
authors.forename: Isabel
authors.initials: I
authors.lastname: Guerrero
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002462:Cell Membrane / Q000378:metabolism; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D004848:Epithelium / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D009024:Morphogenesis; D009154:Mutation; D021381:Protein Transport; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D014921:Wings, Animal / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011509:Proteoglycans; D011956:Receptors, Cell Surface; C403224:disp protein, Drosophila; C420997:dlp protein, Drosophila; C510880:iHog protein, Drosophila; D049452:Green Fluorescent Proteins; C077245:hh protein, Drosophila