16 Wnt regulation of limb muscle differentiation

The limb musculature arises by delamination of premyogenic cells from the lateral dermomyotome. Initially the cells express Pax-3 and are uncommitted to myogenic differentiation, but upon entering the limb field they become committed switching on the expression of MyoD and Myf5. The myogenic cells subsequently undergo terminal differentiation into slow or fast fibre types which have distinct contractile properties determining how a muscle will function. In general, fast fibre types contract rapidly with high force and are needed for movement whilst slow fibre types contract slowly and are largely required for maintenance of posture. During migration, and in the limb bud, the myogenic cells come within range of Wnt signals. Here we have investigated the role of Wnt signalling in the developing chick limb by gain- and loss-of-function studies in vitro and in vivo. We show that Wnt-3a and the Wnt antagonist Sfrp-2 reduce the number of terminally differentiated cells whilst Wnt-7a and -14 have the converse effect. Wnt signalling also changes the number of fast and/or slow fibre types: Wnt-11 decreases and increases the number of slow and fast fibre types respectively whilst Wnt-5a and -6 have the opposite effect. Therefore Wnt signalling is essential for the formation of the limb musculature controlling both the number of terminally differentiated myogenic cells and the ratio of slow and fast fibres determining the intricate patterning of the limb musculature.