Heparan sulfate (HS) proteoglycans (for example, perlecan) are involved in many developmental processes, particularly those regulated by fibroblast growth factors (FGFs). HS regulates FGF activity by acting as an FGF co-receptor at the cell surface and as an FGF reservoir in the extracellular matrix. FGF10 signalling is critical for salivary gland development in mammals and now, on ,Matthew Hoffman and colleagues report that the cleavage of perlecan by heparanase modulates FGF10 activity during branching morphogenesis in the mouse submandibular gland (SMG). They show that the inhibition of heparanase in organ culture decreases SMG branching and that the addition of FGF10, but not other FGFs, rescues branching. Heparanase, they report, releases FGF10 from the basement membrane, where it binds to perlecan. Importantly, the HS fragment that heparanase releases from perlecan also increases FGF10's bioactivity, which increases branching complexity in the SMG. Thus,heparanase, by releasing an HS fragment and FGF10 from the basement membrane,plays a key role in salivary gland development.
