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RESEARCH PAPER

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

¹ Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA , ² Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA , ³ Department of Craniofacial Development, King's College London, Guy's Hospital, London Bridge, London SE1 9RT, UK

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.

[Keywords: Skeletal myogenesis; cranial neural crest; head mesoderm; Wnt; BMP; Noggin; Gremlin; Frzb]

Received September 22, 2003; revised version accepted October 30, 2003.

⁴ Present address: Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, 76100, Israel.

⁵ These authors contributed equally to this work.

⁶ Corresponding author.
E-MAIL andrew_lassar{at}hms.harvard.edu; FAX (617) 738-0516.

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