Fig. 8. Model shows release of FGF10-bound HS fragments from perlecan by heparanase in the basement membrane. HS fragments modulate the biological activity of FGF10 by increasing FGF10-FGFR2b complex formation to promote MAPK phosphorylation, end bud growth and clefting, and lateral branch formation. Syndecan 1 in the epithelium binds FGF10-FGFR2b, and we speculate (grey text) that other unidentified epithelial HSPG may specify the location of lateral buds or end bud clefting. Epithelial HSPGs may form a signaling complex with FGFR2b, in combination with HS fragments released by heparanase, and increase MAPK or other intracellular signaling.