Craniofacial Muscles

20 I. Harel and E. Tzahor
in the head, cranial neural crest cells may also be involved in producing the signals
necessary for the patterning of the head musculature (Couly et al. 1992 ; Ericsson
et al. 2004 ; Grammatopoulos et al. 2000 ; Grenier et al. 2009 ; Heude et al. 2010 ;
Kontges and Lumsden 1996 ; Noden 1983a, b ; Olsson et al. 2001 ; Rinon et al. 2007 ;
Schilling and Kimmel 1997 ; Tokita and Schneider 2009 ; Tzahor et al. 2003 ) .
Because skeletal muscles in the head, except for EOM, still form (albeit in a
distorted fashion), following in vivo ablation of the cranial neural crest cells in
amphibian and chick embryos (Ericsson et al. 2004 ; Olsson et al. 2001 ; Tzahor et al.
2003 ; von Scheven et al. 2006 , reviewed in Noden and Trainor 2005 ) , the precise
impact of cranial neural crest cells on head muscle formation remains unclear. Thus,
while it is generally accepted that the cranial neural crest cells in fl uence cranial
muscle formation, exactly how cranial neural crest cells participate in this process
has yet to be elucidated. The current view in the fi eld is that cranial neural crestderived
connective tissue progressively imposes the characteristic anatomical musculoskeletal
architecture upon PM muscle progenitors (Heude et al. 2010 ; Rinon
et al. 2007 ; Tokita and Schneider 2009 ) .
PM progenitors are exposed to signals from pharyngeal arch endoderm, ectoderm,
and neural crest cells that together create a complex regulatory system
(reviewed in Rochais et al. 2009 ; Vincent and Buckingham 2010 ) . Perturbation of
the balance of signals within this system can lead to abnormal cardiac and craniofacial
development (see below). Neural crest ablation in the chick, for example, results
in increased FGF signaling and elevated proliferation in the PM (Hutson et al. 2006 ;
Rinon et al. 2007 ; Waldo et al. 2005 ) . These fi ndings suggest that both cardiac neural
crest (affecting caudal PM progenitors) and cranial neural crest cells (affecting
cranial PM) buffer proliferative signals (presumably FGFs) secreted from the endoderm
and ectoderm, to promote PM migration and differentiation.
2.8 The Link Between Heart and Pharyngeal-Arch Derived
Muscle Development
The skeletal myogenic potential of PM cells and their contribution to pharyngeal
arch-derived muscles have long been documented (Noden and Francis-West 2006 ;
Wachtler and Jacob 1986 ) . In contrast, the cardiogenic potential of these cells has
only been revealed over the last decade (reviewed in Black 2007 ; Buckingham
et al. 2005 ; Dyer and Kirby 2009 ; Evans et al. 2010 ; Tzahor and Evans 2011 ;
Vincent and Buckingham 2010 ) . For example, PM explants dissected from early
chick embryos undergo cardiogenesis (Nathan et al. 2008 ; Tirosh-Finkel et al.
2006 ; Tzahor and Lassar 2001 ) . The in vivo cardiogenic potential of PM was further
revealed in chick embryos (Nathan et al. 2008 ; Rana et al. 2007 ; Tirosh-Finkel
et al. 2006 ) . It has been shown that Wnt signaling (e.g., Wnt1 and Wnt3a from the
dorsal neural tube) inhibit PM-derived cardiogenesis (Nathan et al. 2008 ; Tzahor
and Lassar 2001 ) . Considerable overlap in the expression of head muscle markers
(e.g., Myf5 , Tcf21 ( capsulin ), Msc ( MyoR ), Tbx1 , Pitx2 ) and cardiac markers such