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PNAS 108 (31): 12591-12598

Copyright © 2011 by the National Academy of Sciences.

From the Cover

FEATURE ARTICLE / BIOLOGICAL SCIENCES / CELL BIOLOGY

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

Ainhoa Callejo, Aphrodite Bilioni, Emanuela Mollica, Nicole Gorfinkiel, Germán Andrés, Carmen Ibáñez, Carlos Torroja, Laura Doglio, Javier Sierra, and Isabel Guerrero1

Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autónoma de Madrid, Cantoblanco, E-28049 Madrid, Spain

This Feature Article is part of a series identified by the Editorial Board as reporting findings of exceptional significance.

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.

Edited by Matthew P. Scott, Stanford University/Howard Hughes Medical Institute, Stanford, CA, and approved May 13, 2011 (received for review April 29, 2011)

Author contributions: I.G. designed research; A.C., A.B., E.M., N.G., G.A., C.I., C.T., L.D., J.S., and I.G. performed research; A.C., N.G., and L.D. contributed new reagents/analytic tools; A.C., A.B., N.G., G.A., C.T., and I.G. analyzed data; and A.C., A.B., and I.G. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

See Commentary on page 12565.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1106881108/-/DCSupplemental.

1To whom correspondence should be addressed. E-mail: iguerrero{at}cbm.uam.es.

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