Dispatched Sends Hedgehog On Its Way

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Science  14 Jan 2000:
Vol. 287, Issue 5451, pp. 193
DOI: 10.1126/science.287.5451.193h

Developmental patterning of the Drosophila wing requires the morphogen Hedgehog (Hh), which is secreted by posterior (P) compartment cells and acts at short range on a narrow strip of anterior (A) cells at the A/P border. Binding of released Hh to Patched (Ptc) serves to sequester Hh at the A/P border and to trigger subsequent signaling steps which are transduced by Smoothened. The appropriate localization of Hh also requires a post-translational modification in which cholesterol is covalently attached to the protein.

Burke et al. report that release of cholesterol-modified Hh is mediated by a protein called Dispatched (Disp). Like Ptc, Disp is a transmembrane protein containing a sterol-sensing domain, a motif found in proteins that regulate cholesterol metabolism. How Disp liberates Hh from P cells is not clear, but it appears to be specific for the cholesterol-tagged form of Hh because an artificial Hh construct containing a different membrane anchor was not released. Although Ptc and Disp are structurally similar, they perform seemingly opposite tasks in that the former sequesters Hh while the latter is required to release the morphogen.—LDC

Cell99, 803 (1999).

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