Neural tube derived signals and Fgf8 act antagonistically to specify eye versus mandibular arch muscles

Abstract

Recent knockout experiments in the mouse generated amazing craniofacial skeletal muscle phenotypes. Yet none of the genes could be placed into a molecular network, because the programme to control the development of muscles in the head is not known. Here we show that antagonistic signals from the neural tube and the branchial arches specify extraocular versus branchiomeric muscles. Moreover, we identified Fgf8 as the branchial arch derived signal. However, this molecule has an additional function in supporting the proliferative state of myoblasts, suppressing their differentiation, while a further branchial arch derived signal, namely Bmp7, is an overall negative regulator of head myogenesis.

Dynamic control of head mesoderm patterning

“…This expression pattern was maintained at later stages (shown for HH16, Fig. 1A-Eix) and represents the mature, pharyngula-stage pattern described previously for the chicken (Roberts et al, 2005;Tirosh-Finkel et al, 2006;von Scheven et al, 2006a;von Scheven et al, 2006b) with corresponding expression in the mouse (Kelly et al, 2004;Lu et al, 2002;Shih et al, 2007). Taken together (Fig.…”

“…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).…”

“…Bone morphogenetic (Bmp) molecules have been shown to recruit head mesoderm cells to the heart (Tirosh-Finkel et al, 2006) (for reviews, see Rochais et al, 2009;Tzahor, 2009). Yet, Bmp molecules can repress myogenic differentiation without the activation of cardiac markers (von Scheven et al, 2006a). 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).…”

“…Yet, Bmp molecules can repress myogenic differentiation without the activation of cardiac markers (von Scheven et al, 2006a). 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).…”

Cranial muscle defects of Pitx2 mutants result from specification defects in the first branchial arch

“…The intermandibularis helps pump air to the lung in amphibians and is thought to correspond to the mylohyoid and anterior digastic in mammals. Grafting studies suggested that development of mastication muscles shared distinct and highly conserved genetic pathways from fish to mammals (31). Interestingly, in lamprey, a jawless fish with strong mastication muscles, the Pitx2 and Tbx1 orthologous genes are also expressed in first BA mesodermal core (32,33).…”