Fgf4 Positively Regulates scleraxis and Tenascin Expression in Chick Limb Tendons

Abstract

In vertebrates, tendons connect muscles to skeletal elements. Surgical experiments in the chick have underlined developmental interactions between tendons and muscles. Initial formation of tendons occurs autonomously with respect to muscle. However, further tendon development requires the presence of muscle. The molecular signals involved in these interactions remain unknown. In the chick limb, Fgf4 transcripts are located at the extremities of muscles, where the future tendons will attach. In this paper, we analyse the putative role of muscle-Fgf4 on tendon development. We have used three general tendon markers, scleraxis, tenascin, and Fgf8 to analyse the regulation of these tendon-associated molecules by Fgf4 under different experimental conditions. In the absence of Fgf4, in muscleless and aneural limbs, the expression of the three tendon-associated molecules, scleraxis, tenascin, and Fgf8, is down-regulated. Exogenous implantation of Fgf4 in normal, aneural, and muscleless limbs induces scleraxis and tenascin expression but not that of Fgf8. These results indicate that Fgf4 expressed in muscle is required for the maintenance of scleraxis and tenascin but not Fgf8 expression in tendons.

Anterior cruciate ligament-derived cells have high chondrogenic potential

“…In the limb buds, diversification of cartilage and ligament/tendon lineages is regulated by antagonism between BMP and fibroblast growth factor (FGF) signaling pathways [33]. BMP-2 not only promotes chondrogenesis, but also inhibits ligament/tendon development, while FGF-4 has the opposite effect [34]. The BMP inhibitor Noggin represses the expression of Sox9 while inducing the Scx expression [35].…”

Expression of scleraxis and tenascin C in equine adipose and umbilical cord blood derived stem cells is dependent upon substrata and FGF supplementation

“…Fibroblast growth factors are required for proper syndetome formation and induction of tenocytic lineage (Brent and Tabin 2004;Edom-Vovard et al 2002). As such, the response of adipose and UCB derived stem cells to FGFs was investigated.…”

“…FGFs produced by the myotome supply a paracrine signal that allows formation of the sclerotome and syndetome (Brent and Tabin 2004). Exogenous FGF4 induces scleraxis and tenascin C mRNA synthesis in the developing chick limb (Edom-Vovard et al 2002). Ectopic expression of FGF5 in chick embryos inhibited skeletal muscle growth and promoted proliferation of tenascin C immunopositive fibroblasts in the hind limb (Clase et al 2000).…”

Tubulin polymerization‐promoting protein family member 3, Tppp3, is a specific marker of the differentiating tendon sheath and synovial joints

“…Detection of Scx expression through embryonic development unraveled early aspects of tendon development and enabled analysis of early events in tendon induction and differentiation (Schweitzer et al, 2001;Edom-Vovard et al, 2002;Brent et al, 2003;Brent and Tabin, 2004). To facilitate analysis of tendon phenotypes, a robust tendon reporter mouse, ScxGFP, was subsequently generated, in which expression of eGFP is driven by regulatory elements of the Scx gene (Pryce et al, 2007).…”