title: Cytonemes are required for the establishment of a normal Hedgehog morphogen gradient in Drosophila epithelia.
abstract: Hedgehog (Hh) signalling is important in development, stem cell biology and disease. In a variety of tissues, Hh acts as a morphogen to regulate growth and cell fate specification. Several hypotheses have been proposed to explain morphogen movement, one of which is transport along filopodia-like protrusions called cytonemes. Here, we analyse the mechanism underlying Hh movement in the wing disc and the abdominal epidermis of Drosophila melanogaster. We show that, in both epithelia, cells generate cytonemes in regions of Hh signalling. These protrusions are actin-based and span several cell diameters. Various Hh signalling components localize to cytonemes, as well as to punctate structures that move along cytonemes and are probably exovesicles. Using in vivo imaging, we show that cytonemes are dynamic structures and that Hh gradient establishment correlates with cytoneme formation in space and time. Indeed, mutant conditions that affect cytoneme formation reduce both cytoneme length and Hh gradient length. Our results suggest that cytoneme-mediated Hh transport is the mechanistic basis for Hh gradient formation.
authors.affiliation: Department of Zoology, University of Cambridge, Downing Street, Cambridge, CB2 3EJ, UK.
authors.forename: Marcus
authors.initials: M
authors.lastname: Bischoff
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Nicolas Cabrera 1, Universidad Autónoma de Madrid, Cantoblanco, E-28049 Madrid, Spain.
authors.forename: Ana-Citlali
authors.initials: AC
authors.lastname: Gradilla
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Nicolas Cabrera 1, Universidad Autónoma de Madrid, Cantoblanco, E-28049 Madrid, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Seijo
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Nicolas Cabrera 1, Universidad Autónoma de Madrid, Cantoblanco, E-28049 Madrid, Spain.
authors.forename: Germán
authors.initials: G
authors.lastname: Andrés
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Nicolas Cabrera 1, Universidad Autónoma de Madrid, Cantoblanco, E-28049 Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Rodríguez-Navas
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Nicolas Cabrera 1, Universidad Autónoma de Madrid, Cantoblanco, E-28049 Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: González-Méndez
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Nicolas Cabrera 1, Universidad Autónoma de Madrid, Cantoblanco, E-28049 Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Guerrero
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D004847:Epithelial Cells / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014921:Wings, Animal / Q000166:cytology / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D053823:Hedgehog Proteins; C077245:hh protein, Drosophila