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Title: The role of the Hippo co-activators Yap, Taz and Vgll in regulating muscle cell fate and embryonic development
Author: De Mello, Vanessa Chantelle
ISNI:       0000 0004 6056 8773
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2016
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The Hippo pathway is a master regulator of cell proliferation and organ size, namely through regulation of transcriptional co-activators Yap, Taz, Vgll family which bind Tead1-4 transcription factors. Recently the Hippo pathway has been shown to regulate muscle cell fate. Yap enhances the proliferation of myoblasts and inhibits their differentiation, Taz comparatively enhances both aspects. The mechanisms in which they regulate muscle cell fate and muscle development are poorly defined. In this thesis I determined the endogenous gene expression of Hippo transcription factors during myogenesis. Secondly their proteomic binding partners in myoblasts and myotubes. Thirdly, the gene sets targeted by YAP1 S127A, TAZ S89A and Vgll3 in myoblasts. Finally, I cloned chicken Yap1 to identify its role during embryonic muscle development, followed by retroviral YAP1 S127A overexpression during chicken embryonic limb development. The results demonstrated that the Hippo transcriptional regulators are mainly up-regulated during muscle regeneration in vivo. YAP1 and TAZ were mainly found to regulate the same gene sets and have the same binding partners. TAZ additionally had unique binding partners and gene sets that may promote muscle differentiation. Furthermore, Vgll3 also had many overlapping genes with YAP and TAZ, suggesting it is part of the Hippo pathway, but negatively regulates Hippo pathway gene expression. Yap expression during chicken embryonic development was observed in muscle related regions including the somites and limb buds. However, retroviral overexpression of YAP S127A did not lead to an overt phenotype but still up-regulated transcription musculoskeletal related genes. Collectively my data provides insight into how the Hippo transcriptional regulators control myogenesis, their binding partners and their transcription targets. Additionally, have characterised the expression of chicken Yap during embryonic muscle development.
Supervisor: Not available Sponsor: Biotechnology and Biological Sciences Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Muscle cells ; Myogenesis