Heparan sulfate is essential for Drosophila FGF export

Binding of Fibroblast growth factor (FGF) to a heparan sulfate proteoglycan (HSPG) is required for paracrine FGF signaling. To improve our understanding of FGF:HSPG association, we developed a method to monitor export of the Drosophila FGF ortholog Branchless (Bnl) in vivo . We detected Bnl on the surface of approximately 10% of Bnl-producing cells, but Bnl on the surface of cells depleted of HS was much reduced. HS depletion also non-autonomously decreased the activity of cytonemes that extend from cells that receive Bnl. These results are consistent with the idea that Bnl export to the cell surface is regulated, that intracellular binding of an HSPG to Bnl in producing cells is essential for export, and that cells that take up Bnl actively participate in its release from producing cells. Summary Levels of FGF exported to the surface of FGF-expressing cells are dependent on intracellular heparan sulfate proteoglycans.