Antagonists of Wnt and BMP signaling promote the formation of vertebrate head muscle.
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.
Tzahor
Eldad
E
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Kempf
Hervé
H
Mootoosamy
Roy C
RC
Poon
Andy C
AC
Abzhanov
Arhat
A
Tabin
Clifford J
CJ
Dietrich
Susanne
S
Lassar
Andrew B
AB
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016466:CHO Cells / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins; D002642:Chick Embryo; D003391:Cranial Nerves / Q000378:metabolism; D006224:Cricetinae; D046508:Culture Techniques; D004627:Embryonic Induction / Q000502:physiology; D006023:Glycoproteins / Q000494:pharmacology*; D006257:Head; D053823:Hedgehog Proteins; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D008648:Mesoderm / Q000166:cytology / Q000502:physiology; D024510:Muscle Development / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology*; D009432:Neural Crest / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D000099176:Noggin Protein; D000099274:Frizzled-Related Proteins
D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D006023:Glycoproteins; D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D000099176:Noggin Protein; D000099274:Frizzled-Related Proteins