Abstract
Vertebrate body shape depends on precise three-dimensional (3D) alignment of individual tissues which themselves have a defined 3D shape, but it is still unknown how this is achieved. Understanding the mechanisms by which 3D organs are generated and aligned is important for the improvement of regenerative medicine, which aims to facilitate 3D tissue/organ formation. A genome-wide medaka (Oryzias latipes) mutagenesis screen identified the hirame (hir) mutant, which has a point mutation in the WW1 protein domain of the Yes-associated protein (YAP) gene. The hir mutant exhibits a pronounced flattened body in which individual organs collapse and are not properly aligned. These features of the mutant make it an ideal model organism for the study of how individual 3D tissues/organs are developed and how they align coordinately to generate the global body shape.In this study, YAP function in an intact mutant animal was analysed by various means, including immunohistochemistry (IHC) and time-lapse confocal microscopy, revealling a previously unrecognised crucial role for YAP. This study demonstrates that a single gene product governs the global 3D body shape by mediating not only cell behaviour within the tissue for production of its 3D morphology but also coordinated morphogenesis of adjacent tissues through ECM assembly around the tissues. Further in vivo and in vitro analyses demonstrated that the function of YAP is most likely regulated by actomyosin-mediated tissue tension.
| Date of Award | 20 May 2015 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Makoto Furutani-Seiki (Supervisor) & Stefan Bagby (Supervisor) |
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