FGF acts directly on the somitic tendon progenitors through the Ets transcription factorsPea3andErmto regulate scleraxis expression

Abstract

During somite development, a fibroblast growth factor (FGF) signal secreted from the myotome induces formation of a scleraxis (Scx)-expressing tendon progenitor population in the sclerotome, at the juncture between the future lineages of muscle and cartilage. While overexpression studies show that the entire sclerotome is competent to express Scx in response to FGF signaling, the normal Scx expression domain includes only the anterior and posterior dorsal sclerotome. To understand the molecular basis for this restriction, we examined the expression of a set of genes involved in FGF signaling and found that several members of the Fgf8synexpression group are co-expressed with Scx in the dorsal sclerotome. Of particular interest were the Ets transcription factors Pea3 and Erm, which function as transcriptional effectors of FGF signaling. We show here that transcriptional activation by Pea3and Erm in response to FGF signaling is both necessary and sufficient for Scx expression in the somite, and propose that the domain of the somitic tendon progenitors is regulated both by the restricted expression of Pea3 and Erm, and by the precise spatial relationship between these Ets transcription factors and the FGF signal originating in the myotome.

In vitro and in vivo effects of PDGF-BB delivery strategies on tendon healing: a review

“…So far, PDGF involvement in tendon development has not been described. TGFβ (specifically TGFβ2/3) and FGF (specifically FGF4 and FGF8) signalling are shown to play a role in collagen expression/synthesis during development and in adult life (Brent and Tabin, 2004;Kuo et al, 2008;Mikic et al, 2006;Paxton et al, 2012;Yun et al, 2010). Tendon differentiation is mediated through the Smad signalling pathway of TGFβ (Lorda-Diez et al, 2009;Pryce et al, 2009).…”

“…Tendon differentiation is mediated through the Smad signalling pathway of TGFβ (Lorda-Diez et al, 2009;Pryce et al, 2009). Disruption of FGF and TGFβ signalling leads to expression inhibition of the tendon associated transcription factor scleraxis (Scx) (Brent and Tabin, 2004;Brent et al, 2005;EdomVovard et al, 2002;Pryce et al, 2009). Scx is a basic helix-loop-helix transcription factor, involved in regulating expression of other tenogenic markers such as tenascin-C, tenomodulin, Mohawk and type I collagen.…”

BMP and FGF regulatory pathways in semilunar valve precursor cells

“…Less is known about the roles of FGF signaling during heart valve development, but several FGF ligands, including FGF4 and downstream signaling molecules, are expressed in the heart during cushion formation (Karabagli et al, 2002;Sugi et al, 2003;Liberatore and Yutzey, 2004;Lincoln et al, 2006a). These expression patterns support the importance of FGF signaling in regulating gene expression of tendon-associated genes during cell lineage diversification, consistent with the FGF and dpERK activation of scleraxis in the developing somites (Sugi et al, 2003;Brent and Tabin, 2004;Smith et al, 2005). The significant activation of dpERK1/2 in response to FGF4 treatment (or inhibition of BMP signaling) in semilunar valve precursor cells, strongly suggests that as shown in developing AV valves, FGF signaling through ERK1/2 phosphorylation regulates expression of scleraxis and tenascin (Lincoln et al, 2006a).…”

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).…”