The molecular setup of the avian head mesoderm and its implication for craniofacial myogenesis

Abstract

The head mesoderm is the mesodermal tissue on either side of the brain, from forebrain to hindbrain levels, and gives rise to the genuine head muscles. Its relatedness to the more posterior paraxial mesoderm, the somites, which generate the muscles of the trunk, is conversely debated. To gain insight into the molecular setup of the head mesoderm, its similarity or dissimilarity to the somitic mesoderm, and the implications of its setup for the progress of muscle formation, we investigated the expression of markers (1) for mesoderm segmentation and boundary formation, (2) for regional specification and somitogenesis and (3) for the positive and negative control of myogenic differentiation. We show that the head mesoderm is molecularly distinct from somites. It is not segmented; even the boundary to the first somite is ill-defined. Importantly, the head mesoderm lacks the transcription factors driving muscle differentiation while genes suppressing differentiation and promoting cell proliferation are expressed. These factors show anteroposteriorly and dorsoventrally regionalised but overlapping expression. Notably, expression extends into the areas that actively contribute to the heart, overlapping with the expression of cardiac markers.

Dynamic control of head mesoderm patterning

“…Details of probes have been published previously: Alx4,chordin,Cyp26C1,Isl1,Myf5,MyoR,Nkx2.5,paraxis,Pax3,Pitx2,Raldh2,Tbx1 and Twist (see Bothe and Dietrich, 2006);Bmp2, Bmp7, Fgf4, Fgf8 and Fgf10 (see Lours and Dietrich, 2005;von Scheven et al, 2006a); Bmp4 (see Francis et al, 1994); follistatin and noggin (see Chapman et al, 2002); Hoxb1 (see Bell et al, 1999); Mkp3 (Pyst) (see Eblaghie et al, 2003).…”

“…However, factors that control somite formation in the trunk are absent in the head (Bothe and Dietrich, 2006). The key regulator of somitic myogenesis, Pax3, is not expressed in the head mesoderm either (Bothe and Dietrich, 2006;Hacker and Guthrie, 1998;Mootoosamy and Dietrich, 2002).…”

“…However, factors that control somite formation in the trunk are absent in the head (Bothe and Dietrich, 2006). The key regulator of somitic myogenesis, Pax3, is not expressed in the head mesoderm either (Bothe and Dietrich, 2006;Hacker and Guthrie, 1998;Mootoosamy and Dietrich, 2002). Within the MyoD family of muscle determination factors, Mrf4 can compensate for the absence of Myf5 or MyoD in somitic, but not head, muscle formation (Kassar-Duchossoy et al, 2004).…”

“…Recent studies revealed that the head mesoderm expresses a unique set of marker genes (Bothe and Dietrich, 2006). These genes, Pitx2, Alx4, MyoR (musculin) and Tbx1, label and pattern the tissue prior to the onset of differentiation; they also distinguish head-derived muscle satellite cells (adult muscle stem cells) from satellite cells in the trunk (Harel et al, 2009;Sambasivan et al, 2009).…”

“…Fibroblast growth factors (Fgfs) have been placed upstream of both Tbx1 and MyoR (Abu-Issa et al, 2002;Mitsiadis et al, 2008;von Scheven et al, 2006a). However, initially Tbx1 and MyoR are expressed in different anteroposterior domains (Bothe and Dietrich, 2006). Most of the experiments addressing the control of head mesodermal gene expression have been performed at late neurulation (HH8-9) or early organogenesis stages (HH10-12), and phenotypes were analysed at pharyngula stages of development when the formation of the heart as well as individual muscle anlagen is well under way.…”