Craniofacial Muscles

2 Head Muscle Development
21
as Islet1 and Nkx2.5 has been documented in the PM, suggesting that these cells
play a dual role in myogenesis and cardiogenesis (Bothe and Dietrich 2006 ; Nathan
et al. 2008 ; Tirosh-Finkel et al. 2006 ) . Likewise, lineage studies in the mouse demonstrated
an overlap in progenitor populations contributing to pharyngeal muscles
and second heart fi eld derivatives (Dong et al. 2006 ; Harel et al. 2009 ; Nathan et al.
2008 ; Verzi et al. 2005 ) . Thus, the genetic program controlling development of
pharyngeal arch-derived muscles overlaps with that controlling the PM-derived
heart progenitors.
The LIM-homeodomain protein Islet1 (Isl1) is required for a broad subset of
cardiac progenitors in the mouse (Cai et al. 2003 ; Laugwitz et al. 2008 ; Lin et al.
2007 ; Sun et al. 2007 ) . Gene expression and lineage experiments in the chick have
revealed that the core of the pharyngeal arch is divided along the proximal–distal
axis, such that paraxial mesoderm cells mainly contribute to the proximal region of
the core, while the splanchnic mesoderm contributes to its distal region (Nathan
et al. 2008 ) . Isl1 is expressed in the distal part of the PM, and its expression is correlated
with delayed differentiation of lower jaw muscles (Nathan et al. 2008 ) .
Over-expression of Isl1 in the chick represses pharyngeal muscle differentiation
(Harel et al. 2009 ) .
Lineage tracing experiments in the mouse, using an Isl1 Cre line revealed the
signi fi cant contribution of Isl1 + cells to the mesodermal core of the pharyngeal
arches (Harel et al. 2009 ; Nathan et al. 2008 ) , as well as to the heart (Moretti et al.
2006 ) . Isl1 + PM cells were shown to contribute to a subset of pharyngeal arch-derived
muscles (mylohyoid, stylohyoid, and digastric) at the base of the mandible, facilitating
its opening. Isl1 + cells give rise to PA2 muscles controlling facial expression
(Harel et al. 2009 ; Nathan et al. 2008 ) and, to a lesser extent, the masseter, pterygoid,
and temporalis, the jaw closing muscles, indicating that this gene is not expressed
in all PM progenitors. In both species, tongue and EOM are not derived from the
Isl1 lineage (Harel et al. 2009 ; Nathan et al. 2008 ) . Taken together, Isl1 marks a
subset of PM cells, and plays an important role in the development of distinct
PM-derived cardiovascular and skeletal muscle progenitors (Tzahor and Lassar
2001 ) . The direct role of Isl1 in pharyngeal arch-derived muscle development has
yet to be resolved, as Isl1 knockout embryos die at around E10 (Cai et al. 2003 ) .
A retrospective clonal analysis in the mouse, developed in the Buckingham lab,
demonstrated recently that head muscles and second heart fi eld derivatives originate
from multipotent PM progenitors (Lescroart et al. 2010 ) . Two myogenic lineages
that link groups of head muscles to different parts of the heart were identi fi ed. The
fi rst muscle lineage gives rise to the temporalis and masseter as well as to the EOM.
Strikingly, this single cell clone also contributes to myocardial cells in the right
ventricle. The second lineage gives rise to a broad range of muscles controlling
facial expression, which derive from PA2 mesoderm, and also contributes myocardial
cells at the arterial pole of the heart (Lescroart et al. 2010 ) . In conclusion, this
study and others provide cellular and molecular insights into how pharyngeal
mesoderm cells form distinct pharyngeal arch-derived muscles and certain parts of
the heart.