Changes in the expression of fibroblast growth factor receptors mark distinct stages of chondrogenesis in vitro and during chick limb skeletal patterning

Abstract

Members of the fibroblast growth factor (FGF) family of growth factors are key regulators of limb skeletal patterning and growth. Abnormal expression of FGFs or mutations in their receptors (fgfrs) result in skeletal disorders. Here we show that changes in the expression of f&s are intrinsic properties of differentiating cartilage. In mesenchymal micromass cultures differentiating into cartilage, as in ovo, fgfr 1 mRNA was found predominantly in undifferentiated, proliferating mesenchyme, f& 2 in precartilage cell aggregates, and fgfi-3 in differentiating cartilage nodules. Thus, our data suggest that switches in the expression of fgfr 1, 2, and 3 mRNAs are associated with phases of cartilage patterning both in vitro and in ovo, and mark distinct stages in the development of the limb skeleton. o 1995 Wiley-Lisa, Inc.

FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease

“…3A). These patterns of expression have been observed in chicken, mouse, and hu- man limb development (Orr-Urtreger et al 1991;Peters et al 1992;Szebenyi et al 1995;Delezoide et al 1998). Later in skeletal development, Fgfr1 and Fgfr2 expression persists in the perichondrium and periosteum in patterns that suggest expression in the osteoblast lineage .…”

Fibroblast growth factors 2 and 4 stimulate migration of mouse embryonic limb myogenic cells

“…We compared the expression pattern of FGF-2 and Pax-3 and found that migrating myogenic cells were capable of expressing FGF-2. Moreover, these cells also expressed FREK, the FGF receptor (Marcelle et al, 1995;Szebenyi et al, 1995). Because our Blindwell chemotactic assays showed that FGF-2 can stimulate chemokinesis as well as chemotaxis, it is possible that myogenic cells maintain their own ability to migrate in the limb by producing FGF-2, which then acts through some form of autocrine mechanism.…”

Fibroblast growth factor signaling in skeletal development and disease

“…1A) Fgfr2 expression is increased (compared with the surrounding mesenchyme) and initially overlaps with domains of Sox9 expression (Orr-Urtreger et al 1991;Peters et al 1992;Szebenyi et al 1995;Delezoide et al 1998;Eswarakumar et al 2002;Sheeba et al 2010). Fgfr1 is more uniformly expressed throughout limb bud mesenchyme.…”

“…Fgfr1 is more uniformly expressed throughout limb bud mesenchyme. Although Fgfr3 and Fgfr4 are excluded from distal limb bud mesenchyme, these Fgfrs are expressed in more proximal locations in tissues corresponding to developing muscle (OrrUrtreger et al 1991;Peters et al 1992;Szebenyi et al 1995;Delezoide et al 1998;Sheeba et al 2010). Cells in the periphery of the condensation that will form perichondrium and periosteum express both Fgfr1 and Fgfr2 ( Fig.…”