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 the in vivo export of Drosophila Branchless (Bnl), an FGF ortholog. We detected Bnl on the surface of ∼10% of Bnl-producing cells, and the amount of Bnl was reduced on the surface of cells depleted of heparan sulfate (HS). 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 not constitutive, that intracellular Bnl:HSPG binding in producing cells is essential for FGF export, and that cells that take up Bnl actively participate in its release from producing cells.