The aims of this thesis were to 1) investigate the effect of SB431542 <i>in vitro</i> and <i>ex vivo</i> as a novel approach towards promoting the functional hypertrophy of skeletal muscle by inhibiting the myostatin-Smad pathway, 2) to investigate the expression and function of the Yes-associated protein (Yap) in skeletal muscle and C2C12 cells as a novel regulator of C2C12 differentiation and 3) to generate a GFP-RCASBP-hYAP1 S127A retrovirus to allow the study of the function of Yap in skeletal muscle differentiation <i>in vivo</i>. The results presented in this thesis show that SB431542 promotes the hypertrophy of C2C12 myotubes and mature <i>Xenopus</i> skeletal muscle fibres. However, SB431542 treatment also results in a reduction in specific force of mature <i>Xenopus</i> muscle fibres suggesting that SB431542 is not suitable as a treatment for skeletal muscle atrophy. These results also show that Yap is expressed in mouse skeletal muscle <i>in vivo</i> and that Yap is a novel regulator of C2C12 differentiation. Finally, these results descried the generation of a GFP-RCASBP-hYAP1 S127A retrovirus that can be used to assess the role of Yap <i>in vivo </i>during skeletal muscle formation in the chick embryo. Together, these results suggest that Yap is a novel regulator of C2C12 differentiation that should be studied as a potential therapeutic target in musculoskeletal diseases.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:522334 |
| Date | January 2009 |
| Creators | Watt, Kevin |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=62160 |
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