Heparan sulfate is essential for Drosophila FGF export

Area of Science:

• Cell biology
• Developmental biology
• Biochemistry

Background:

• Paracrine Fibroblast Growth Factor (FGF) signaling is crucial for development and relies on binding to heparan sulfate proteoglycans (HSPG).
• Understanding the precise mechanisms of FGF:HSPG interaction and FGF export is essential for elucidating signaling pathways.

Purpose of the Study:

• To develop a method for monitoring the *in vivo* export of the Drosophila FGF ortholog, Branchless (Bnl).
• To investigate the role of heparan sulfate (HS) in Bnl export and its impact on intercellular signaling.

Main Methods:

• Development of an *in vivo* assay to track Bnl export from producing cells in Drosophila.
• Experimental manipulation of HS levels in Bnl-producing cells to assess its effect on Bnl cell surface localization.
• Observation of cytoneme activity in cells receiving Bnl following HS depletion.

Main Results:

• Bnl was detected on the surface of a subset of Bnl-producing cells, indicating regulated export.
• HS depletion significantly reduced Bnl localization on the cell surface.
• HS depletion non-autonomously impaired the activity of cytonemes involved in Bnl uptake.

Conclusions:

• Bnl export to the cell surface is a regulated process.
• Intracellular HSPG binding to Bnl is critical for its export from producing cells.
• Cells actively participate in the release of Bnl from producing cells, highlighting a cooperative signaling mechanism.