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Presenting Author(s) Pip Francis-West
Lesley Robson
Kelly Anakwe
Abstract Title Regulation of limb myogenesis.
Full author List Julia Hadley 1
Text of abstract

Myogenic cells of the limb bud arise by delamination from the lateral dermomyotome of the somite in response to signals from the lateral plate mesoderm and ectoderm. Subsequently, they migrate into the developing limb bud where they become committed to myogenesis, switching on the expression of the myogenic determination genes, Myf5 and MyoD. The committed myoblasts then differentiate further ultimately forming fused myotubes, expressing heavy myosin chains, capable of contraction. Simplistically, the MyHC can be of two types, either slow or fast, and the relative contribution to each muscle will determine how it functions. We have previously shown that members of the Wnt family differentially control myogenic differentiation controlling both the number of myoblasts and terminal differentiation. For example, Wnt5a promotes the development of slow myoblasts, seemingly through a camodulin kinase pathway whilst Wnt11 increases the number of fast myoblasts. In both cases, there was little change in the total number of terminally differentiated myoblasts or myocytes. In contrast, we found that Wnt3a and Wnt7a decreased and increased the number of myocytes respectively. To further understand, how Wnt signalling regulates myogenic cell number, we turned our attention to the paired box transcription factor, Pitx2 which has been shown to be activated in response to Wnt signalling and to regulate myogenic proliferation in the C2C12 satellite cell line. We show that Pitx2 is expressed in developing myogenic cells in the limb bud and that it is necessary for myogenic development. Furthermore, overexpression of Pitx2 increases the number of myoblasts in vitro culture.

Finally, we have examined the role of another transcription factor, Tbx1. This gene marks a subset of myoblasts in the developing limb and loss-of-function studies have again indicated that it is necessary for myogenic differentiation.

Which session is your work most relevant to: Tissue differentiation