Sprouty gene expression is regulated by nerve and FGF6 during regeneration of mouse muscles

Abstract

Sprouty (Spry) proteins were identified as negative regulators of fibroblast growth factor (FGF) signaling in vertebrates and invertebrates. Given the importance of the FGFs in myogenesis, we performed cardiotoxin injury-induced regeneration experiments on soleus muscles of both, adult control and FGF6 ( - / - ) mutant mice and analyzed the accumulation of Spry (1, 2 and 4) transcripts using semi-quantitative and real-time RT-PCR assays and in situ hybridization. We also analyzed the effects of muscle denervation on the accumulation of Spry transcripts. The three Spry genes begin to be expressed as early as the first stages of muscle regeneration and are characterized by distinct expression patterns. Moreover, Spry gene expression was highly and differentially up-regulated, precociously by the lack of FGF6, and belatedly by muscle denervation strongly suggesting that the transient rise of Spry mRNA accumulation was associated to muscle differentiation. Rescue experiments supported the idea of a specific relationship between FGF6 and Spry 2, both being known for their particular involvement in myogenesis.

Sprouty1 Regulates Reversible Quiescence of a Self-Renewing Adult Muscle Stem Cell Pool during Regeneration

“…Low levels of Spry1 expression could be observed in subsets of nascent myotubes in vivo and in vitro (data not shown) as shown previously (Laziz et al, 2007). This likely reflects that Spry genes are activated in the presence of growth factors within the extrinsic milieu and that differentiated myotubes can respond to growth factor signals (Perez-Ruiz et al, 2007).…”

Fgf signaling components are associated with muscles and tendons during limb development

“…This is consistent with the location of mSprouty1 transcripts at the edges of the dermomyotomes and in myotomes in E10.5 mouse embryos (Lagha et al,2008). However, the function of Sprouty genes in myogenesis is not clear, since some studies indicate a contribution of Sprouty genes to myogenic differentiation (de Alvaro et al,2005; Laziz et al,2007), while others conclude that Sprouty prevents myogenic progenitor cells from entering the skeletal differentiation program (Lagha et al,2008).…”

Sprouty2 mediated tuning of signalling is essential for somite myogenesis

“…Our results are consistent with other previously reported localisation of the mouse Spry2 transcripts in the myotomes and dermomyotomes [ 27 ]. In addition, a number of studies have also highlighted the involvement of Spry1 and Spry2 proteins during the myogenic differentiation [ 28 , 29 ].…”

“…In Pax3 knockout mice Sprouty expression was lost indicating that they are expressed in muscle progenitors [ 27 ]. In addition, it has been shown, by using artificial regeneration and rescue experiments in mouse, that FGF6 and Spry2 are particularly involved in myogenesis [ 28 ]. Overexpression of SPRY2 in C2C12 cells in presence of FGF2 led to induction of myogenesis whilst inhibition of SPRY2 function led to myoblasts growth and failure of myotube formation.…”