Wnt signalling regulates myogenic differentiation in the developing avian wing

K Anakwe; L Robson; J Hadley; P Buxton; V Church; S Allen; C Hartmann; B Harfe; T Nohno; A M C Brown; D J R Evans; P Francis-West

doi:10.1242/dev.00538

Wnt signalling regulates myogenic differentiation in the developing avian wing

K Anakwe, L Robson, J Hadley, P Buxton, V Church, S Allen, C Hartmann, B Harfe, T Nohno, A M C Brown, D J R Evans, P Francis-West

Centre for Craniofacial & Regenerative Biology

Research output: Contribution to journal › Article › peer-review

142 Citations (Scopus)

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 11 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.

Original language	English
Pages (from-to)	3503 - 3514
Number of pages	12
Journal	Development (Cambridge): for advances in developmental biology and stem cells
Volume	130
Issue number	15
DOIs	https://doi.org/10.1242/dev.00538
Publication status	Published - Aug 2003

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Anakwe, K., Robson, L., Hadley, J., Buxton, P., Church, V., Allen, S., Hartmann, C., Harfe, B., Nohno, T., Brown, A. M. C., Evans, D. J. R., & Francis-West, P. (2003). Wnt signalling regulates myogenic differentiation in the developing avian wing. Development (Cambridge): for advances in developmental biology and stem cells, 130(15), 3503 - 3514. https://doi.org/10.1242/dev.00538

@article{c8f5864da16c46fcae518d5ffb1a7bd6,

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 11 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.",

author = "K Anakwe and L Robson and J Hadley and P Buxton and V Church and S Allen and C Hartmann and B Harfe and T Nohno and Brown, {A M C} and Evans, {D J R} and P Francis-West",

year = "2003",

month = aug,

doi = "10.1242/dev.00538",

language = "English",

volume = "130",

pages = "3503 -- 3514",

journal = "Development (Cambridge): for advances in developmental biology and stem cells",

issn = "1477-9129",

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Anakwe, K, Robson, L, Hadley, J, Buxton, P, Church, V, Allen, S, Hartmann, C, Harfe, B, Nohno, T, Brown, AMC, Evans, DJR & Francis-West, P 2003, 'Wnt signalling regulates myogenic differentiation in the developing avian wing', Development (Cambridge): for advances in developmental biology and stem cells, vol. 130, no. 15, pp. 3503 - 3514. https://doi.org/10.1242/dev.00538

TY - JOUR

T1 - Wnt signalling regulates myogenic differentiation in the developing avian wing

AU - Anakwe, K

AU - Robson, L

AU - Hadley, J

AU - Buxton, P

AU - Church, V

AU - Allen, S

AU - Hartmann, C

AU - Harfe, B

AU - Nohno, T

AU - Brown, A M C

AU - Evans, D J R

AU - Francis-West, P

PY - 2003/8

Y1 - 2003/8

N2 - 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 11 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.

AB - 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 11 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.

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U2 - 10.1242/dev.00538

DO - 10.1242/dev.00538

M3 - Article

SN - 1477-9129

VL - 130

SP - 3503

EP - 3514

JO - Development (Cambridge): for advances in developmental biology and stem cells

JF - Development (Cambridge): for advances in developmental biology and stem cells

IS - 15

ER -

Wnt signalling regulates myogenic differentiation in the developing avian wing

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