Dispatched mediates Hedgehog basolateral release to form the long-range morphogenetic gradient in the Drosophila wing disk epithelium

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 108; no. 31; pp. 12591 - 12598
• Main Authors: Callejo, Ainhoa, Bilioni, Aphrodite, Mollica, Emanuela, Gorfinkiel, Nicole, Andrés, Germán, Ibáñez, Carmen, Torroja, Carlos, Doglio, Laura, Sierra, Javier, Guerrero, Isabel
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 02.08.2011; National Acad Sciences
• Series: Feature Article
• Subjects: Animals; Animals, Genetically Modified; Antibodies; Biological Sciences; Cell Membrane - metabolism; Cell membranes; Cells; Cholesterols; Cytoplasmic Vesicles - metabolism; Dextrans; Drosophila; Drosophila melanogaster - genetics; Drosophila melanogaster - growth & development; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Epithelium; Epithelium - growth & development; Epithelium - metabolism; Epithelium - ultrastructure; Genetics; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; growth and development; Hedgehog Proteins - genetics; Hedgehog Proteins - metabolism; Immunohistochemistry; Insects; Internalization; Lipids; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; Membranes; Microscopy, Confocal; Microscopy, Immunoelectron; Morphogenesis; Mutation; Plasma interactions; plasma membrane; Protein Transport; Proteins; Proteoglycans - genetics; Proteoglycans - metabolism; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Recycling; RNA Interference; Wings, Animal - growth & development; Wings, Animal - metabolism; Wings, Animal - ultrastructure
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1106881108

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.