Fig. 1.

FGF gradients can regulate the morphogenesis of LG buds. (A, B) A hypothetical model of the regulation of branching morphogenesis by FGFs with different affinities for HS. FGFs applied locally (asterisk) diffuse differently depending on their affinities for HS. (A) An FGF with a high affinity for HS has restricted diffusion (red sector) through the ECM and signals only to those cells (red crosses) that are most proximal to the FGF source resulting in elongation of the bud towards the source. (B) An FGF with low affinity for HS has a much broader diffusion range, which leads to proliferation of cells that are proximal and distal to the FGF source, which results in branching. (C to F) Effects of FGF10 and FGF7 on the growth and migration of the isolated lacrimal bud. Within 24 hours of exposure, buds adjacent to an FGF10-loaded bead elongated towards the bead (C, D), whereas buds adjacent to an FGF7-loaded bead branched instead (E, F) (five independent experiment were performed: 8–10 explants per condition per experiment). (G to J) Gradient formation by, and response of isolated lacrimal buds to, an FGF10-loaded bead in collagen gel in the absence (G and I) or presence (H and J) of soluble heparin. The extended FGF gradient (H) induced branching (J) instead of elongation (five experiments; 8–10 explants per condition per experiment). (K) Four FGF10-loaded beads placed around an LG epithelial bud induced branching (three experiments; 24 explants). (L) Schematic describing an experiment in which LG buds are briefly exposed to soluble FGF10 (red) or BSA (blue) prior to culture near an FGF10-loaded bead. (M to P) Short exposure of whole lacrimal buds (distal and proximal parts) to FGF10 (25 ng/ml) induced branching near the FGF10-loaded bead (L, O, and P), whereas buds treated with BSA migrated towards the bead (L, M, and N) (seven experiments performed; 8–10 explants per condition per experiment).