Myf5 is a direct target of long-range Shh signaling and Gli regulation for muscle specification

Activation of the hedgehog pathway confers a poor prognosis in embryonal and fusion gene-negative alveolar rhabdomyosarcoma

“…Furthermore, our analysis identifies Myf5 as an excellent class predictor for RMS based on the fusion gene status or on histology. Myf5 has been shown to be a downstream target of Gli1 during muscle development, at least in the somite epaxial muscle progenitors in mice (Gustafsson et al, 2002). In addition, its expression is dependent on Gli3 expression during embryonic muscle formation (McDermott et al, 2005).…”

“…As we previously reported that Hh activation interferes with muscle differentiation (Koleva et al, 2005), we also determined expression levels of markers of muscle differentiation, that is, MyoD1 and Myf5 as early markers of muscle differentiation and Myh1 as a late marker (Tomczak et al, 2004). Furthermore, Myf5 is regulated by Hh signaling (Gustafsson et al, 2002;Gerber et al, 2007). Initially, we assessed expression profiles of these markers in a group of 103 RMS patients that we recently characterized (cohort 1) (Williamson et al, 2010).…”

Uncommitted precursor cells might contribute to increased incidence of embryonal rhabdomyosarcoma in heterozygous Patched1-mutant mice

“…The myogenic factor Myf5 determines the onset of myogenic development and labels all myogenic cells at this developmental stage until expression of MyoD commences (Braun et al, 1994;Gensch et al, 2008). In addition, expression of Myf5 in the somites and the hypaxial musculature has been reported to depend on active Hh signaling (Gustafsson et al, 2002;McDermott et al, 2005), which makes Myf5-positive cells an attractive …”

“…The expression of Ptch, which is detected in the presomitic and lateral plate mesoderm and in the somites (Goodrich et al, 1996;Hahn et al, 1996;Resende et al, 2010) overlaps with Myf5 expression in the presomitic and paraxial mesoderm (Gensch et al, 2008), and in the earliest somites in the dermatomyotome (Asakura and Tapscott, 1998). Moreover, Myf5 expression in the myotome has been reported to depend on Hh signaling and its mediators Gli2 and Gli3 in E9.5 and E10.5 mouse embryos (Gustafsson et al, 2002;McDermott et al, 2005). Likewise, development of the hypaxial musculature relies on active Hh signaling (Kruger et al, 2001).…”

“…In fact, Gli1 was overexpressed in the tumors as revealed by quantitative RT-PCR, when compared with normal skeletal muscle (Figure 4a). In addition, Gli2 and Gli3, and their downstream target during embryonic muscle formation, Myf5 (Gustafsson et al, 2002;McDermott et al, 2005), were also strongly expressed in ERMS ( Figure 4a). As the early stages of muscle development seem to be highly susceptible for ERMS development, we also analyzed genes that are differentially expressed by embryonic and fetal myoblasts.…”