title: The ESCRT machinery regulates the secretion and long-range activity of Hedgehog.
abstract: The conserved family of Hedgehog (Hh) proteins acts as short- and long-range secreted morphogens, controlling tissue patterning and differentiation during embryonic development. Mature Hh carries hydrophobic palmitic acid and cholesterol modifications essential for its extracellular spreading. Various extracellular transportation mechanisms for Hh have been suggested, but the pathways actually used for Hh secretion and transport in vivo remain unclear. Here we show that Hh secretion in Drosophila wing imaginal discs is dependent on the endosomal sorting complex required for transport (ESCRT). In vivo the reduction of ESCRT activity in cells producing Hh leads to a retention of Hh at the external cell surface. Furthermore, we show that ESCRT activity in Hh-producing cells is required for long-range signalling. We also provide evidence that pools of Hh and ESCRT proteins are secreted together into the extracellular space in vivo and can subsequently be detected together at the surface of receiving cells. These findings uncover a new function for ESCRT proteins in controlling morphogen activity and reveal a new mechanism for the transport of secreted Hh across the tissue by extracellular vesicles, which is necessary for long-range target induction.
authors.affiliation: 1] Université de Nice Sophia Antipolis, iBV, UMR 7277, 06100 Nice, France [2] CNRS, iBV, UMR 7277, 06100 Nice, France [3] INSERM, iBV, U1091, 06100 Nice, France.
authors.forename: Tamás
authors.initials: T
authors.lastname: Matusek
authors.affiliation: 1] Université de Nice Sophia Antipolis, iBV, UMR 7277, 06100 Nice, France [2] CNRS, iBV, UMR 7277, 06100 Nice, France [3] INSERM, iBV, U1091, 06100 Nice, France.
authors.forename: Franz
authors.initials: F
authors.lastname: Wendler
authors.affiliation: 1] Université de Nice Sophia Antipolis, iBV, UMR 7277, 06100 Nice, France [2] CNRS, iBV, UMR 7277, 06100 Nice, France [3] INSERM, iBV, U1091, 06100 Nice, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Polès
authors.affiliation: 1] Université de Nice Sophia Antipolis, iBV, UMR 7277, 06100 Nice, France [2] CNRS, iBV, UMR 7277, 06100 Nice, France [3] INSERM, iBV, U1091, 06100 Nice, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Pizette
authors.affiliation: 1] Université de Nice Sophia Antipolis, iBV, UMR 7277, 06100 Nice, France [2] CNRS, iBV, UMR 7277, 06100 Nice, France [3] INSERM, iBV, U1091, 06100 Nice, France.
authors.forename: Gisela
authors.initials: G
authors.lastname: D'Angelo
authors.affiliation: 1] Université de Nice Sophia Antipolis, iBV, UMR 7277, 06100 Nice, France [2] CNRS, iBV, UMR 7277, 06100 Nice, France [3] INSERM, iBV, U1091, 06100 Nice, France.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Fürthauer
authors.affiliation: 1] Université de Nice Sophia Antipolis, iBV, UMR 7277, 06100 Nice, France [2] CNRS, iBV, UMR 7277, 06100 Nice, France [3] INSERM, iBV, U1091, 06100 Nice, France.
authors.forename: Pascal P
authors.initials: PP
authors.lastname: Thérond
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism*; D006458:Hemolymph / Q000378:metabolism; D060227:Imaginal Discs / Q000166:cytology / Q000196:embryology; D021381:Protein Transport; D015398:Signal Transduction; D022161:Transport Vesicles / Q000378:metabolism
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D053823:Hedgehog Proteins