Hedgehog movement is regulated through tout velu-dependent synthesis of a heparan sulfate proteoglycan

Hedgehog (Hh) molecules play critical roles during development as a morphog en, and therefore their distribution must be regulated. Hh proteins undergo several modifications that tether them to the membrane. We have previously identified tout velu (ttv), a homolog of the mammalian EXT tumor supressor gene family, as a gene required for movement of Hh. In this paper, we pres ent in vivo evidence that ttv is involved in heparan sulfate proteoglycan ( HSPG) biosynthesis, suggesting that HSPGs control Hh distribution. In contr ast to mutants in other HSPG biosynthesis genes, the activity of the HSPG-d ependent FGF and Wingless signaling pathways are not affected in ttv mutant s. This demonstrates an unexpected level of specificity in the regulation o f the distribution of extracellular signals by HSPGs.