Craniofacial Muscles

16 I. Harel and E. Tzahor
satellite cells (Fig. 2.3b , Harel et al. 2009 ) . In contrast, trunk muscle-associated satellite
cells (including tongue muscles) derive from the Pax3 + lineage; Pax3 + cells and
Pax3 expression are not seen in any other head muscles. In contrast, all head muscles
and their satellite cells derive from the MesP1 + lineage (including the tongue
and EOM), whereas the Isl1 lineage solely marks the pharyngeal arch-derived muscles
and their satellite cells (Harel et al. 2009 ) . In addition to lineage distinction,
differences in gene expression and differentiation potentials were observed between
satellite cells in head vs. trunk-derived muscles (Harel et al. 2009 ; Ono et al. 2010 ;
Sambasivan et al. 2009 ) . Transplantation of myo fi ber-associated head satellite cells
into damaged limb muscle contributed toward ef fi cient muscle regeneration (Harel
et al. 2009 ; Sambasivan et al. 2009 ) . Furthermore, in vitro experiments demonstrated
the cardiogenic nature of head-, but not trunk-derived satellite cells (Harel
et al. 2009 ) . Fewer head satellite cells from the masseter (see Fig. 2.1 ) are seen;
also, these cells are more proliferative, and display delayed differentiation relative
to the timing of differentiation of satellite cells derived from trunk muscles (Ono
et al. 2010 ) . Taken together, these fi ndings highlight a link between myogenesis in
the early embryo and the generation of adult muscle progenitor pools required for
muscle maintenance and regeneration (Fig. 2.3 ).
Heterogeneity in skeletal muscles can also be seen during adulthood, as re fl ected
in distinct genetic signatures and susceptibilities to myopathies in both head and
trunk skeletal muscles (Emery 2002 ; Porter et al. 2006 ) . In humans, several diseases
are characteristic of skeletal muscle tissue, and one of the longstanding mysteries in
the fi eld is why some muscles, but not others, are affected, even though they are
often located in close anatomical proximity. For example, Duchenne Muscular
Dystrophy (DMD), seen in 1/3,500 male births, results in lethality by the time these
individuals reach their mid-twenties, even with extensive intervention and health
care support in the later stages of the disease. Strikingly, in DMD patients, most
muscles are affected; yet EOM and laryngeal muscles are largely spared. This
fi nding re fl ects an underlying theme in muscle diseases: understanding why virtually
all myopathies affect only a subset of muscles is of great scienti fi c interest, with
potential clinical relevance. Hence the phenotypic outcome observed in diverse
myopathies maybe rooted in developmental underpinnings.
2.5 Distinct Genetic Programs in Trunk and Head Muscles
It appears that different intrinsic and extrinsic regulatory pathways control skeletal
muscle formation in the trunk and in the head, as indicated by genetic loss of myogenic
transcription factors in mice (Kelly et al. 2004 ; Lu et al. 2002 ; Rudnicki et al.
1993 ; Tajbakhsh et al. 1997 ) as well as by manipulations of tissues and signaling
molecules in chick embryos (Hacker and Guthrie 1998 ; Mootoosamy and Dietrich
2002 ; Noden et al. 1999 ; Tzahor et al. 2003 ) . While skeletal muscle formation in
both regions of the embryo requires either MyoD or Myf5 (Rudnicki et al. 1993 ) ,
mice lacking both Myf5 and Pax3 are completely devoid of trunk muscles, yet retain