Wnt regulation of embryonic limb and craniofacial muscle differentiation

There is a clear precedent that craniofacial, limb and trunk muscle development are controlled by distinct molecular networks. However, in all cases, muscle differentiation starts with Myf5 and MyoD expression and ends with terminal differentiation characterised by myosin heavy chain expression. The latter can be either slow or fast and the ratio will determine how a muscle will function. Simplistically, fast myocytes are needed for movement whilst slow myocytes are involved in the maintenance of posture. Here we have analysed the role of Wnt signalling, which is essential for trunk muscle development, during limb and craniofacial muscle development. We show that in the limb bud as in the trunk, Wnt/ b‐catenin signalling regulates myocyte number. In addition, we identify an unsuspected role of Wnt signalling during the development of the slow and fast limb myocytes: Wnt5a promotes slow myocyte formation whilst Wnt11 has the converse effect. Likewise in the mandibular primordia, Wnt11 inhibits slow myocyte development. Finally, we have analysed a potential down‐stream mediator of Wnt signalling, the transcription factor Pitx2. We show that Pitx2 is expressed by all developing myoblasts and that it regulates myogenic proliferation.