Developmental Biology

Dispatched Liberates Hedgehog

Science's STKE  11 Jan 2000:
Vol. 2000, Issue 14, pp. tw1
DOI: 10.1126/stke.2000.14.tw1

Morphogenic signals that regulate tissue patterning during development are often secreted molecules that can travel short or long distances from their point of origin. Patterning of the Drosophila wing involves 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. Response to Hh is restricted by the Hh receptor Patched (Ptc), which sequesters Hh to this region of A cells in the wing. Modification of autoproteolytically cleaved Hh with cholesterol is also thought to restrict the effects of Hh by tethering the molecule to cellular membranes. Burke et al. report that release of cholesterol-modified Hh requires that P cells express a protein called Dispatched (Disp). Disp is predicted to have 12 transmembrane domains, and similar to Ptc, has a sterol-sensing domain (SSD), a region found in proteins that regulate cholesterol trafficking. Analysis of Drosophila genetic mosaics indicate that Disp does not regulate the expression or processing of Hh, but functions to release Hh from P cells by a mechanism that is not yet clear. In mutants that did not express Disp, Hh was retained in P cells. Although Ptc and Disp are structurally similar, they perform seemingly opposite tasks in that the former sequesters the morphogen while the latter is required for release of the signaling molecule. The study suggests that lipid anchors may be a mechanism to restrict the range of a morphogenic signal.

Burke, R., Nellen, D., Bellotto, M., Hafen, E., Senti, K-A., Dickson, B.J., and Basler, K. (1999) Dispatched, a novel sterol-sensing domain protein dedicated to the release of cholesterol-modified Hedgehog from signaling cells. Cell 99: 803-815. [Online Journal]