Antagonists of Wnt and BMP signaling promote the formation of vertebrate head muscle

Abstract

Recent studies have postulated that distinct regulatory cascades control myogenic differentiation in the head and the trunk. However, although the tissues and signaling molecules that induce skeletal myogenesis in the trunk have been identified, the source of the signals that trigger skeletal muscle formation in the head remain obscure. Here we show that although myogenesis in the trunk paraxial mesoderm is induced by Wnt signals from the dorsal neural tube, myogenesis in the cranial paraxial mesoderm is blocked by these same signals. In addition, BMP family members that are expressed in both the dorsal neural tube and surface ectoderm are also potent inhibitors of myogenesis in the cranial paraxial mesoderm. We provide evidence suggesting that skeletal myogenesis in the head is induced by the BMP inhibitors, Noggin and Gremlin, and the Wnt inhibitor, Frzb. These molecules are secreted by both cranial neural crest cells and by other tissues surrounding the cranial muscle anlagen. Our findings demonstrate that head muscle formation is locally repressed by Wnt and BMP signals and induced by antagonists of these signaling pathways secreted by adjacent tissues. Vertebrate locomotion crucially depends on trunk skeletal muscles, which all derive from the segmented paraxial mesoderm termed somites (for review, see Christ and Ordahl 1995). During the past decade, the tissues and signaling molecules that induce the formation of skeletal muscle from somites have been intensively studied. These studies have indicated that somitic myogenesis in the trunk is affected by signals emanating from the axial tissues, the surface ectoderm, and the lateral plate mesoderm. Wnt family members expressed in the dorsal neural tube work together with Sonic hedgehog (Shh) expressed in the notochord to activate myogenic bHLH gene expression (that is, Myf-5 and MyoD) in the epaxial component of the myotome (Munsterberg et al. 1995;Stern et al. 1995;Tajbakhsh et al. 1998;Borycki et al. 2000;Gustafsson et al. 2002). In addition, Wnt signals from the dorsal ectoderm have been demonstrated to up-regulate the expression of MyoD in the hypaxial component of the myotome (Tajbakhsh et al. 1998). Furthermore, BMP signals from the lateral plate have been shown to delay the activation of myogenic bHLH gene expression in the hypaxial muscle progenitors relative to those that form the epaxial musculature (Pourquié et al. 1996). In contrast to our understanding of how skeletal muscle is induced in the trunk, the tissues and signaling pathways that induce the formation of skeletal muscle in the head have not yet been elucidated.In the vertebrate head, ∼40 skeletal muscles are present, which, instead of serving for locomotion, rather move the eye, control the cranial openings, or facilitate food uptake and, in humans, speech (for review, see Wachtler and Jacob 1986). Although the hypobranchial muscles, the tongue muscles, and the muscles of the posterior branchial arches (BAs), develop from the somites, the remainder of the head muscles (that is, the "genui...

Spatial relations between avian craniofacial neural crest and paraxial mesoderm cells

“…An early and sustained association would allow for the simultaneous and synchronous modulation of muscle differentiation and muscle morphogenesis by signals from adjacent tissues, including but not limited to the neural crest (Tzahor et al, 2003). Alternatively, precise, nearest-neighbor relations may be unnecessary during the early differentiation stages of myo-genesis.…”

The differentiation and morphogenesis of craniofacial muscles

“…In vitro analyses of head paraxial mesoderm cocultured with individual or combinations of surrounding tissues reveal that factors released by the hindbrain and surface ectoderm depress the ability of mesoderm cells to initiate (or elevate) expression of myf5 (Tzahor et al, 2004). This repression is mediated by Bmps and Wnts from the neural tube and ectoderm.…”

Tbx1 regulation of myogenic differentiation in the limb and cranial mesoderm

“…The morphological difference found during development of the head and trunk myogenic cells is reflected at the transcriptional level and in the signaling cascades that regulate myogenesis (reviewed by Noden and FrancisWest, 2006). In the trunk, Wnt signals are necessary for myogenic development, whereas in the head, they are inhibitory (Tzahor et al, 2003;Chen et al, 2005; reviewed by Buckingham et al, 2003. These distinctions are also associated with a unique repertoire of transcription factors expressed during axial/appendicular versus craniofacial muscle development.…”