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.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:704540 |
| Date | January 2016 |
| Creators | De Mello, Vanessa Chantelle |
| 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=231535 |
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