title: Wnt signalling regulates myogenic differentiation in the developing avian wing.
abstract: The limb musculature arises by delamination of premyogenic cells from the lateral dermomyotome. Initially the cells express Pax3 but, upon entering the limb bud, they switch on the expression of MyoD and Myf5 and undergo terminal differentiation into slow or fast fibres, which have distinct contractile properties that determine how a muscle will function. In the chick, the premyogenic cells express the Wnt antagonist Sfrp2, which is downregulated as the cells differentiate, suggesting that Wnts might regulate myogenic differentiation. Here, we have investigated the role of Wnt signalling during myogenic differentiation in the developing chick wing bud by gain- and loss-of-function studies in vitro and in vivo. We show that Wnt signalling changes the number of fast and/or slow fibres. For example, in vivo, Wnt11 decreases and increases the number of slow and fast fibres, respectively, whereas overexpression of Wnt5a or a dominant-negative Wnt11 protein have the opposite effect. The latter shows that endogenous Wnt11 signalling determines the number of fast and slow myocytes. The distinct effects of Wnt5a and Wnt11 are consistent with their different expression patterns, which correlate with the ultimate distribution of slow and fast fibres in the wing. Overexpression of activated calmodulin kinase II mimics the effect of Wnt5a, suggesting that it uses this pathway. Finally, we show that overexpression of the Wnt antagonist Sfrp2 and DeltaLef1 reduces the number of myocytes. In Sfrp2-infected limbs, the number of Pax3 expressing cells was increased, suggesting that Sfrp2 blocks myogenic differentiation. Therefore, Wnt signalling modulates both the number of terminally differentiated myogenic cells and the intricate slow/fast patterning of the limb musculature.
authors.affiliation: Department of Craniofacial Development, King's College, London SE1 9RT, UK.
authors.forename: Kelly
authors.initials: K
authors.lastname: Anakwe
authors.forename: Lesley
authors.initials: L
authors.lastname: Robson
authors.forename: Julia
authors.initials: J
authors.lastname: Hadley
authors.forename: Paul
authors.initials: P
authors.lastname: Buxton
authors.forename: Vicki
authors.initials: V
authors.lastname: Church
authors.forename: Steve
authors.initials: S
authors.lastname: Allen
authors.forename: Christine
authors.initials: C
authors.lastname: Hartmann
authors.forename: Brian
authors.initials: B
authors.lastname: Harfe
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nohno
authors.forename: Anthony M C
authors.initials: AM
authors.lastname: Brown
authors.forename: Darrell J R
authors.initials: DJ
authors.lastname: Evans
authors.forename: Philippa
authors.initials: P
authors.lastname: Francis-West
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002642:Chick Embryo; D004627:Embryonic Induction / Q000502:physiology; D005810:Multigene Family; D024510:Muscle Development / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014921:Wings, Animal / Q000196:embryology*; D051153:Wnt Proteins; D029961:Zebrafish Proteins
chemical_list: D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D029961:Zebrafish Proteins