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doi: 10.1242/10.1242/dev.00538
1 Department of Craniofacial Development, King's College, London SE1 9RT,
UK
2 Department of Neuroscience, Bart's and The London, Queen Mary's School of
Medicine and Dentistry, London E1 4NS, UK
3 Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
4 Department of Molecular Biology, Kawasaki Medical School, 577 Matsushima,
Kurashiki, 701-0192, Japan
5 Department of Cell and Developmental Biology, Weill Medical College of Cornell
University and Strang Cancer Prevention Center, New York, NY 10021, USA
6 School of Biosciences, Cardiff University, Cardiff CF10 3US, UK
Author for correspondence (e-mail:
pfrancis{at}hgmp.mrc.ac.uk)
Accepted 8 April 2003
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 
Lef1 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.
Key words: Wnt, Limb, Myogenic differentiation, Fibre type, Chick
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