Setting the Hedgehog gradient

Morphogenetic gradients control many developmental patterning events in Drosophila and vertebrates but how these gradients are established is unclear. Torroja and co-workers report that Patched (Ptc), the receptor for the morphogen Hedgehog (Hh), regulates the Hh gradient in the Drosophila wing imaginal disc by mediating its endocytosis (see p. 2395). The researchers use mutations that block the endocytic pathway at different points to show that Ptc internalises Hh in a dynamin-dependent manner, and that internalised Hh and Ptc are targeted for lysosomal degradation. The researchers also test whether the two proposed functions of Ptc - activation of Hh signalling and sequestration of Hh - can be genetically uncoupled. In the ptc¹⁴ mutant, in which Hh is not endocytosed,expression of Hh target genes is normal, leading the researchers to conclude that Ptc-mediated Hh internalisation does not have a major role in Hh signal transduction.