ROLE OF FGFS IN SKELETAL-MUSCLE AND LIMB DEVELOPMENT

Fibroblast growth factors (FGFs) are a family of nine proteins that bi nd to three distinct types of cell surface molecules: (i) FGF receptor tyrosine kinases (FGFR-1 through FGFR-4); (ii) a cysteine-rich FGF re ceptor (CFR); and (iii) heparan sulfate proteoglycans (HSPGs). Signali ng by FGFs requires participation of at least two of these receptors: the FGFRs and HSPGs form a signaling complex. The length acid sulfatio n pattern of the heparan sulfate chain determines both the activity of the signaling complex and, in part, the ligand specificity for FGFR-1 . Thus, the heparan sulfate proteoglycans are likely to play an essent ial role in signaling. We have recently identified a role for FGF in l imb bud development in vivo. In the chick limb bud, ectopic expression of the 18 kDa form of FGF-2 or FGF-2 fused to an artificial signal pe ptide at its amino terminus causes skeletal duplications. These data, and the observations that FGF-2 is localized to the subjacent mesoderm and the apical ectodermal ridge in the early developing limb, suggest that FGF-2 plays an important role in limb outgrowth. We propose that FGF-2 is an apical ectodermal ridge-derived factor that participates in limb outgrowth and patterning. (C) 1994 Wiley-Liss, Inc.