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Title: Regulation of myogenesis and skeletal muscle size by the myostatin-Smad and mammalian Hippo signalling transduction pathways
Author: Watt, Kevin
ISNI:       0000 0004 2692 800X
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2009
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The aims of this thesis were to 1) investigate the effect of SB431542 in vitro and ex vivo 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 in vivo. The results presented in this thesis show that SB431542 promotes the hypertrophy of C2C12 myotubes and mature Xenopus skeletal muscle fibres. However, SB431542 treatment also results in a reduction in specific force of mature Xenopus 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 in vivo 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 in vivo 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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Musculoskeletal system ; Muscles ; Muscle, Skeletal