Glypican-mediated endocytosis of Hedgehog has opposite effects in flies and mice

Glypicans are glycosylphosphatidylinositol-linked heparan sulfate proteoglycans that play an essential part in the regulation of morphogen signalling. Two new reports using Drosophila and mice have highlighted the importance of glypican endocytosis in the regulation of Hedgehog (Hh) signalling and in Wingless gradient formation. One Drosophila glypican, Dally-like, acts positively in Hh signalling, whereas mouse Glypican-3 is a negative regulator. This difference seems to be dependent on whether glypicans promote the internalization of Hh alone or as a complex with its receptor, Patched.