Research ArticleMorphogenesis

Differential Interactions of FGFs with Heparan Sulfate Control Gradient Formation and Branching Morphogenesis

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Science Signaling  15 Sep 2009:
Vol. 2, Issue 88, pp. ra55
DOI: 10.1126/scisignal.2000304

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Branch or Elongate

The graded distribution of morphogens, such as fibroblast growth factors (FGFs), is critically important for the patterning of tissues in the developing embryo. Binding of morphogens to heparan sulfate glycosaminoglycans (HSGAGs) controls their diffusion through the extracellular matrix (ECM); however, the extent to which these interactions modulate the activities of morphogens is unclear. Makarenkova et al. studied the differential effects of FGF7 and FGF10, two closely related FGFs with different biological activities, in the context of branching morphogenesis of epithelia from mouse embryonic lacrimal and submandibular glands. Whereas FGF7 induces branching of epithelial buds, FGF10 induces their elongation. Replacement of a single residue in the heparan-binding site of FGF10 with the corresponding residue of FGF7 resulted in a mutant FGF10 that acted as a functional mimic of FGF7; it diffused more readily into the ECM than did wild-type FGF10 and it induced branching rather than elongation of epithelial buds. Thus, not only are the gradients of morphogens established by their interactions with HSGAGs, but these interactions can also modulate their biological activities.

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