title: Balancing Hedgehog, a retention and release equilibrium given by Dally, Ihog, Boi and shifted/DmWif.
abstract: Hedgehog can signal both at a short and long-range, and acts as a morphogen during development in various systems. We studied the mechanisms of Hh release and spread using the Drosophila wing imaginal disc as a model system for polarized epithelium. We analyzed the cooperative role of the glypican Dally, the extracellular factor Shifted (Shf, also known as DmWif), and the Immunoglobulin-like (Ig-like) and Fibronectin III (FNNIII) domain-containing transmembrane proteins, Interference hedgehog (Ihog) and its related protein Brother of Ihog (Boi), in the stability, release and spread of Hh. We show that Dally and Boi are required to prevent apical dispersion of Hh; they also aid Hh recycling for its release along the basolateral part of the epithelium to form a long-range gradient. Shf/DmWif on the other hand facilitates Hh movement restrained by Ihog, Boi and Dally, establishing equilibrium between membrane attachment and release of Hh. Furthermore, this protein complex is part of thin filopodia-like structures or cytonemes, suggesting that the interaction between Dally, Ihog, Boi and Shf/DmWif is required for cytoneme-mediated Hh distribution during gradient formation.
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), C/Nicolas Cabrera 1, Universidad Autónoma de Madrid, Cantoblanco, E-28049 Madrid, Spain.
authors.forename: Aphrodite
authors.initials: A
authors.lastname: Bilioni
authors.forename: David
authors.initials: D
authors.lastname: Sánchez-Hernández
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Callejo
authors.forename: Ana-Citlali
authors.initials: AC
authors.lastname: Gradilla
authors.forename: Carmen
authors.initials: C
authors.lastname: Ibáñez
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mollica
authors.forename: M
authors.initials: M
authors.lastname: Carmen Rodríguez-Navas
authors.forename: Eléanor
authors.initials: E
authors.lastname: Simon
authors.forename: Isabel
authors.initials: I
authors.lastname: Guerrero
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D005786:Gene Expression Regulation; D005838:Genotype; D049452:Green Fluorescent Proteins / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence / Q000379:methods; D008954:Models, Biological; D008957:Models, Genetic; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D019076:Transgenes
chemical_list: C555140:Boi protein, Drosophila; D002352:Carrier Proteins; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D011956:Receptors, Cell Surface; C576538:Shf protein, Drosophila; C098128:dally protein, Drosophila; C510880:iHog protein, Drosophila; D049452:Green Fluorescent Proteins