The secreted morphogen sonic hedgehog (Shh) and other hedgehog (Hh) proteins control many aspects of normal development through short- and long-range signalling. But, before being released from its source cells, two lipid moieties are added to Shh that probably make it insoluble, so how does Shh signal over long distances? Henk Roelink and colleagues report that dispatched 1 (Disp1, a twelve-transmembrane protein that resembles the Shh receptor patched 1, Ptch1) plays a role in long-range Shh signalling in vertebrate cells (see p. ). In polarised epithelial cells, they report, Disp1 function is required for the basolateral secretion of Shh, and Ptch1 on adjacent cells is required for Shh uptake. By measuring the Shh response in neuralised mouse embryoid bodies with and without Disp1 function, they show that the Shh signalling range is shortened in Disp1−/− tissue, even when Shh is produced by co-cultured Disp1-expressing cells. Together, these results suggest that reiterated Disp1-dependent Shh secretion, coupled to Ptch1-dependent Shh uptake, distributes Shh through tissues rather than long-range diffusion.
