Role of FGFs in skeletal muscle and limb development.
Fibroblast growth factors (FGFs) are a family of nine proteins that bind to three distinct types of cell surface molecules: (i) FGF receptor tyrosine kinases (FGFR-1 through FGFR-4); (ii) a cysteine-rich FGF receptor (CFR); and (iii) heparan sulfate proteoglycans (HSPGs). Signaling by FGFs requires participation of at least two of these receptors: the FGFRs and HSPGs form a signaling complex. The length and sulfation 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 essential role in signaling. We have recently identified a role for FGF in limb 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 peptide 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.
Olwin
B B
BB
Department of Biochemistry, Purdue University, West Layfayette, Indiana.
Arthur
K
K
Hannon
K
K
Hein
P
P
McFall
A
A
Riley
B
B
Szebenyi
G
G
Zhou
Z
Z
Zuber
M E
ME
Rapraeger
A C
AC
D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002454:Cell Differentiation; D002455:Cell Division; D002642:Chick Embryo; D005346:Fibroblast Growth Factors / Q000378:metabolism / Q000502:physiology*; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000737:chemistry / Q000378:metabolism; D008648:Mesoderm / Q000502:physiology*; D008969:Molecular Sequence Data; D009132:Muscles / Q000166:cytology / Q000196:embryology*; D010012:Osteogenesis; D011509:Proteoglycans / Q000737:chemistry / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000502:physiology*; D015398:Signal Transduction; D014921:Wings, Animal / Q000196:embryology*
D005346:Fibroblast Growth Factors; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D011509:Proteoglycans; D017468:Receptors, Fibroblast Growth Factor