Heparan sulphate proteoglycans (HSPGs), which contain a core protein decorated with polysaccharide chains of glycosaminoglycan (GAG) disaccharide units, modulate the activity of many developmentally important growth factors. In Drosophila embryos, for example, they regulate Hedgehog (Hh) and Wingless (Wg) signalling. Now, surprisingly, Bornemann and co-workers reveal that HSPGs play no role in BMP signalling in early fly embryos despite their well-known role in BMP signalling in larval imaginal discs (see ). HSPGs are absent during the first 3 hours of embryonic development when the BMP gradient(which controls dorsoventral patterning) is established, they report. This is because early HSPG synthesis is prevented by a translational block of GAG synthesis that involves developmentally regulated internal ribosome entry sites (IRESs); this block is lifted when Hh and Wg signalling starts. IRES-like features are conserved in the transcripts of GAG synthesis enzymes from diverse organisms, the researchers note. Thus, translational control of HSPG synthesis might be an evolutionarily conserved way to modulate growth factor signalling.
