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Cell fate determination during development often requires morphogen transport from producing to distant responding cells. Hedgehog (Hh) morphogens present a challenge to this concept, as all Hhs are synthesized as terminally lipidated molecules that form insoluble clusters at the surface of producing cells. While several proposed Hh transport modes tie directly into these unusual properties, the crucial step of Hh relay from producing cells to receptors on remote responding cells remains unresolved. Using wing development in Drosophila melanogaster as a model, we show that Hh relay and direct patterning of the 3–4 intervein region strictly depend on proteolytic removal of lipidated N-terminal membrane anchors. Site-directed modification of the N-terminal Hh processing site selectively eliminated the entire 3–4 intervein region, and additional targeted removal of N-palmitate restored its formation. Hence, palmitoylated membrane anchors restrict morphogen spread until site-specific processing switches membrane-bound Hh into bioactive forms with specific patterning functions., eLife digest Each cell in a developing embryo receives information that determines what type of body structure it will form. In fruit flies, this information is partly given by a protein called Hedgehog. In the embryo cells that receive it, Hedgehog can trigger a series of events which activate certain genes and thereby regulate structure formation. The Hedgehog proteins are produced by a different organizing group of cells: from there they transport within the embryo, creating a gradient. Depending on where a responding cell is in the embryo, it receives a different amount of Hedgehog, which gives the cell its identity. For example, Hedgehog proteins form a gradient across a fruit fly’s developing wing, which creates a visible vein pattern. How Hedgehog proteins form gradients is enigmatic, however, because once produced, they cling to the cells that created them. The reason for this unusual behavior is that the two ends of the Hedgehog protein are attached to a different fat molecule. In particular, one extremity is linked to a fat molecule called palmitate. These ends’ fatty additions anchor Hedgehog to the cells that produced them. Then, the tethered proteins gather together to form chain-like clusters where they inactivate each other: the extremity with the palmitate ‘hides’ the portion of the neighboring protein that binds to the receiving cells. It is still unclear how Hedgehog can be activated and released to reach these faraway cells. One hypothesis is that an enzyme comes to the clusters and frees the proteins by cutting both of Hedgehog’s fatty anchors. Thanks to how the palmitate tethers Hedgehog to the cell, the protein is positioned in such a way that when the enzyme makes its snip, the binding site on the neighboring Hedgehog gets exposed: this protein is activated and, when also cut by the enzyme, released. Here, Schürmann et al. create an array of mutant Hedgehog proteins – for example some without palmitate, some with palmitate that cannot be removed by the enzyme – and study how they affect the development of the wing’s pattern in the fruit fly. Coupled with the imaging of the clusters, these experiments support the hypothesis that the palmitate anchor is necessary so that Hedgehog proteins can be turned on before diffusing away. The Hedgehog family of proteins is also present in humans, where it presides over the development of the embryo but is also involved in cancer. Understanding how Hedgehog works in the fruit fly could lead to new discoveries in humans too.